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Investigating the potential of macrophage efferocytosis has led to a growing interest in exploiting macrophage in immunotherapy. Macrophage‐specific nano‐medicines are currently being developed to stimulate the phagocytic clearance of apoptotic debris in atherosclerosis; however, these unnatural nanoparticles exhibit poor biocompatibility and limited efferocytosis activation ability. Here a pro‐efferocytosis biomimetic nanorobot UM‐EVLipo is developed based on nano‐motor and extracellular vesicles (EVs) hybridized with plaque double‐targeted liposomes. An elegant procedure with only 4 steps is integrated to prepare and purify these hybrid nanovesicles. It is first demonstrated that the EVs derived from bone marrow macrophages stimulated with IL‐4 can promote the transformation of M0 and M1 macrophages into M2, an efferocytosis phenotype. Furthermore, the EVs hybridized with SHP‐1 siRNA‐liposomes blocked the “don't eat me” signal from apoptotic debris by intervening CD47‐SIRPα‐SHP‐1 axis. This two‐pronged strategy of resetting phenotype and blocking checkpoints furthest activates macrophage efferocytosis. Importantly, the urease motor increased the swimming speed of nanovesicles in the blood by 12.4 times, making it easier for them to penetrate the endothelial barrier. The UM‐EVLipo accumulated within the atherosclerotic plaque, reactivate lesioned efferocytosis and reduce the plaque area in the carotid and coronary, which demonstrates the potential of a two‐pronged strategy to prevent atherosclerotic cardiovascular disease. [ABSTRACT FROM AUTHOR]

Atherosclerosis, a major global health concern with high morbidity and mortality rates, involves complex interactions of chronic inflammation, oxidative stress, and proteolytic enzymes. Conventional imaging methods struggle to capture the dynamic biochemical processes in atherosclerotic plaques. Here, we introduce a novel unimolecular photoacoustic probe (UMAPP) designed with specific binding sites for neutrophil elastase (NE) and the redox pair O2⋅−/GSH, enabling real‐time monitoring of oxidative stress and activated neutrophils in plaques. UMAPP, comprising a boron‐dipyrromethene (BODIPY) core linked to a hydrophilic NE‐cleavable tetrapeptide and dual oxidative stress‐responsive catechol moieties, facilitates NE‐mediated modulation of photoinduced electron transfer impacting photoacoustic intensity at 685 nm (PA685). Furthermore, oxidation and reduction of catechol groups by O2⋅− and GSH induce reversible, ratiometric changes in the photoacoustic spectrum (PA745/PA685 ratio). Initial UMAPP applications successfully distinguished atherosclerotic and healthy mice, evaluated pneumonia's effect on plaque composition and verified the probe's effectiveness in drug‐treatment studies by detecting molecular alterations before visible histopathological changes. The integrated molecular imaging capabilities of UMAPP offer promising advancements in atherosclerosis diagnosis and management, enabling early and accurate identification of vulnerable plaques. [ABSTRACT FROM AUTHOR]

Background: Carotid atherosclerotic ischemic stroke threatens human health and life. The aim of this study is to establish a radiomics model of perivascular adipose tissue (PVAT) around carotid plaque for evaluation of the association between Peri-carotid Adipose Tissue structural changes with stroke and transient ischemic attack. Methods: A total of 203 patients underwent head and neck computed tomography angiography examination in our hospital. All patients were divided into a symptomatic group (71 cases) and an asymptomatic group (132 cases) according to whether they had acute/subacute stroke or transient ischemic attack. The radiomic signature (RS) of carotid plaque PVAT was extracted, and the minimum redundancy maximum correlation, recursive feature elimination, and linear discriminant analysis algorithms were used for feature screening and dimensionality reduction. Results: It was found that the RS model achieved the best diagnostic performance in the Bagging Decision Tree algorithm, and the training set (AUC, 0.837; 95%CI: 0.775, 0.899), testing set (AUC, 0.834; 95%CI: 0.685, 0.982). Compared with the traditional feature model, the RS model significantly improved the diagnostic efficacy for identifying symptomatic plaques in the testing set (AUC: 0.834 vs. 0.593; Z = 2.114, p = 0.0345). Conclusion: The RS model of PVAT of carotid plaque can be used as an objective indicator to evaluate the risk of plaque and provide a basis for risk stratification of carotid atherosclerotic disease. [ABSTRACT FROM AUTHOR]

Atherosclerosis (AS) is the leading cause of coronary heart disease, which is the primary cause of death worldwide. Recent studies have identified disulfidptosis as a new type of cell death that may be involved in onset and development of many diseases. However, the role of disulfidptosis in AS is not clear. In this study, bioinformatics analysis and experiments in vivo and in vitro were performed to evaluate the potential relationship between disulfidptosis and AS. AS-related sequencing data were obtained from the Gene Expression Omnibus (GEO). Bioinformatics techniques were used to evaluate differentially expressed genes (DEGs) associated with disulfidptosis-related AS. Hub genes were screened using least absolute shrinkage and selection operator (LASSO) and random forests (RF) methods. In addition, we established a foam cell model in vitro and an AS mouse model in vivo to verify the expressions of hub genes. In addition, we constructed a diagnostic nomogram with hub genes to predict progression of AS. Finally, the consensus clustering method was used to establish two different subtypes, and associations between subtypes and immunity were explored. As the results, 9 disulfidptosis-related AS DEGs were identified from GSE28829 and GSE43292 datasets. Evaluation of DEGs using LASSO and RF methods resulted in identification of 4 hub genes (CAPZB, DSTN, MYL6, PDLIM1), which were analyzed for diagnostic value using ROC curve analysis and verified in vitro and in vivo. Furthermore, a nomogram including hub genes was established that accurately predicted the occurrence of AS. The consensus clustering algorithm was used to separate patients with early atherosclerotic plaques and patients with advanced atherosclerotic plaques into two disulfidptosis subtypes. Cluster B displayed higher levels of infiltrating immune cells, which indicated that patients in cluster B may have a positive immune response for progression of AS. In summary, disulfidptosis-related genes including CAPZB, DSTN, MYL6, and PDLIM1 may be diagnostic markers and therapeutic targets for AS. In addition, these genes are closely related to immune cells, which may inform immunotherapy for AS. [ABSTRACT FROM AUTHOR]

Background and aims: Dysfunction of endothelial cells represents a crucial aspect in the pathogenesis of atherosclerosis. The aim of this study was to explore the protective effects of alisol A on vascular endothelial cells and its possible mechanisms. Methods: An atherosclerosis model was established by feeding ApoE-/- mice with high-fat chow. Alisol A (150 mg/kg/d) or atorvastatin (15 mg/kg/d) was administered, and the levels of blood lipids were evaluated. The effect of the drugs on atherosclerotic plaques was observed by staining the aorta with Sudan IV. In vitro experiments were conducted using human aortic endothelial cells (HAECs) to assess the effects of alisol A on cell proliferation, migration, tubulation, secretion, and cellular integrity by CCK-8 assay, wound healing assay, angiogenesis assay, NO secretion, and release of LDH. Transcriptomics and molecular docking were used to explore the mechanism of plaque inhibition and stabilization by alisol A. Results: Alisol A significantly reduced the aortic plaque area in ApoE−/− mice fed with high-fat chow. In vitro , alisol A had a protective effect on HAECs, which was reflected in the inhibition of vascular endothelial cell proliferation, promotion of NO secretion by vascular endothelial cells, inhibition of vascular endothelial cell migration and angiogenesis, and the maintenance of cell membrane integrity. Therefore, alisol A inhibited and stabilized atherosclerotic plaques and slowed down the process of atherosclerosis. Transcriptomics studies showed 4,086 differentially expressed genes (DEGs) in vascular endothelial cells after alisol A treatment. Enrichment analysis indicated that many genes involved in TNF signaling pathway were differentially expressed, and inflammatory genes were suppressed. The molecular docking results verified the hypothesis that alisol A has a low binding energy after docking with TNF target, and TNF could be a potential target of alisol A. Conclusion: Alisol A produced protection on vascular endothelial cells, achieving inhibition and stabilization of atherosclerotic plaques. [ABSTRACT FROM AUTHOR]

We described a rare case of acute ischemic stroke due to calcified cerebral emboli from calcified carotid plaque (CCP). Radiological examinations revealed that the CCP had an irregular configuration containing a calcified nodule and scattered spotty calcifications, and a large calcified plate. The patient underwent carotid endarterectomy to prevent embolic recurrence. Histopathological examination confirmed the presence of an erupted plaque with a disrupted fibrous cap. Calcified nodular protrusion and spotty calcifications in CCP are predictive of a high risk of embolic stroke with plaque rupture. Thus, careful treatment strategies are crucial to prevent the CCP-related embolic recurrence. [ABSTRACT FROM AUTHOR]

AbstractWe investigated serum concentrations of specific inflammatory parameters in patients with significant carotid artery stenosis (CAS) of 50–99%, with an additional focus on patients with moderate stenosis (50–69%), in terms of both symptomatic status and plaque morphology, to determine whether there are certain parameters that can be associated with plaque instability before the progression of CAS to a high degree. The study included 119 CAS patients, 29 of whom had moderate stenosis, and 46 controls. Ultrasonography of the carotid arteries was performed using color flow Doppler and B-mode duplex ultrasound, and serum inflammatory parameters were measured using commercially available enzyme immunoassays. When comparing patients with 50–99% stenosis, only serum amyloid A (SAA) was higher in symptomatic patients, while in the group of patients with 50–69% stenosis, myeloperoxidase (MPO) was higher and pentraxin-3 (PTX-3) was lower in symptomatic compared to asymptomatic patients, and soluble urokinase plasminogen activator receptor (suPAR) was higher in patients with carotid plaque of unstable compared to stable morphology. Our results suggest that the importance of different inflammatory parameters in patients with moderate CAS is not the same as in CAS patients in general, and therefore their separate investigation in patients with high and moderate stenosis may be beneficial. SAA has the potential to be further considered in research to predict CAS symptom risk. There is a possibility that MPO and PTX-3 play a role in the development of CAS symptoms originating from less stenotic plaques and that suPAR is involved in the destabilisation of such plaques. [ABSTRACT FROM AUTHOR]

Atherosclerosis is a chronic lipid-driven inflammatory disease characterized by infiltration of large numbers of macrophages. The progression of the disease is closely related to the status of macrophages in atherosclerotic plaques. Recent advances in plaque analysis have revealed a subpopulation of macrophages that express high levels of triggering receptor expressed on myeloid cells 2 (TREM2). Although TREM2 is known to play a critical role in inflammation, lipid metabolism, and tissue repair, its role in atherosclerosis is still not fully understood. Recent studies have shown that TREM2 promotes macrophage cholesterol uptake and efflux, enhances efferocytosis function, regulates inflammation and metabolism, and promotes cell survival, all of which are significant functions in atherosclerosis. In early plaques TREM2 promotes lipid uptake and increases lesion size. In advanced plaques TREM2 promotes macrophage survival and increases plaque stability. The dualistic nature of TREM2 in atherosclerosis, where it can exert both protective effect and a side effect of increased lesion size, presents a complex but crucial area of study. Understanding these dual roles could help in the development of new therapeutic strategies to modulate TREM2 activity and utilize its atheroprotective function while mitigating its deleterious effects. In this review, we discuss the roles and mechanisms of TREM2 during different stages of atherosclerotic plaques, as well as the potential applications of TREM2 in the diagnosis and treatment of atherosclerosis. [ABSTRACT FROM AUTHOR]

This review focuses on the epigenetic factors that play a vital role in the formation of plaques and lead to atherosclerosis and related diseases in humans during current times. Apart from the epigenetics there are plenty more factors that influence the atherosclerotic risk in the older population of the current era. Lack of physical activities has become one of the most commonly found traits that causes obesity in people especially the middles aged adults. People working 9 - 5 in an office, or an IT firm tend spend idle time with their computer for 4 - 5 consecutive hours with barely changing their position. Lack of exercise tends to affect not only the physical health but also stress a person mentally. Chronic inflammatory diseases like atherosclerosis have a major role in the morbidity and mortality from cardiovascular disease worldwide. Atherosclerotic plaques are created by the pathophysiological process of lipids, inflammatory cells and fibrous components gradually accumulating within artery walls. Endothelial dysfunction signals the start of atherosclerosis and allows low-density lipoproteins (LDL) to enter the subendothelial region. Oxidative stress-induced changes in retained low-density lipoprotein (LDL) set off an inflammatory cascade that draws T cells and monocytes to the site of the lesion. The interaction of these immune cells with the local vascular cells encourages the production of foam cells, which fills the plaque's centre with lipids. Smooth muscle cells multiply and help produce fibrous caps as the lesion ages, which affects the stability of the plaque. Studies shows how the brain responds to physical labour and how differently the effectively the enzymes and hormones are secreted, and their actions are vastly guided based on the physical stress an individual undergoes. Among the most prominent causes of atherosclerosis epigenetics has been focused majorly in this review, where we focus on the underlying genetic factors that play a vital role in atherosclerosis and related cardiovascular diseases and also the genetic approach to a treatment is also elaborated. A number of miRNAs are involved in the cause/cure for the atherosclerosis, the following tables give an outlook regarding the same. This review aims to focus on the causes, risk factors, pathophysiology and the treatment and therapies that are currently available all the way concentrating on the genetic approach in the above-mentioned perspective. [ABSTRACT FROM AUTHOR]

The introduction of CT scans and the subsequent Agatston score in the 1990s drastically improved our ability to detect coronary artery calcification (CAC). This led to its incorporation into cardiovascular risk assessment guidelines set forth by organizations such as the American Heart Association (AHA) and the American College of Cardiology (ACC). Over time, these guidelines have evolved significantly, reflecting an increasing understanding of CAC. Physical activity has become a key factor in the management of cardiovascular disease. However, the relationship between physical activity and CAC remains complex. Although physical activity is generally beneficial for cardiovascular health, paradoxically, high levels of physical activity have been associated with elevated CAC scores. However, these higher CAC levels may indicate the presence of more stable, calcified plaques that provide protection against plaque rupture. These contradictory findings call for balanced interpretations that acknowledge the cardiovascular benefits of physical activity. This review examines the historical development of clinical guidelines for CAC, the paradoxical relationship between physical activity and CAC, and potential underlying mechanisms. It emphasizes the need for future research to utilize objective measures and consistent methodologies to better understand the relationship between physical activity and CAC. [ABSTRACT FROM AUTHOR]

Cholesterol crystal embolism (CCE) is an underrecognized multisystemic disease caused by the displacement of cholesterol crystals from atheromatous aortic plaques to distal vascular beds, leading to ischemic injury of target organs, particularly the kidneys, i.e., atheroembolic renal disease (ARD). According to recent research, cellular necrosis, induced by crystal-induced cytotoxicity, enhances the autoinflammatory cascade of the NLPR3 inflammasome, leading in turn to the so-called "necroinflammation". The purported involvement of the latter in CCE offers a rationale for the therapeutic approach with anti-inflammatory drugs such as glucocorticoids, the use of which has long been a matter of debate in CCE. Diagnostic delay and no consistent evidence regarding efficacious treatment, leading to inconsistency in clinical practice, may worsen the already poor prognosis of ARD. The possible role of glucocorticoids in the treatment of ARD is thereby herein explored in a narrative fashion, analyzing the limited data from case reports and clinical trials. [ABSTRACT FROM AUTHOR]

Objectives: The present study aimed to examine the role of two-dimensional shear wave elastography (SWE) in the assessment of the vascular wall of the carotid arteries and atherosclerotic plaques in patients with rheumatoid arthritis with moderate and low disease activity versus healthy controls. Methods: An observational case–control study was carried out at the University Medical Hospital "Kaspela" in Plovdiv, Bulgaria, from June 2023 to August 2024. This study included 24 patients with rheumatoid arthritis (RA) and 25 healthy controls. We employed two-dimensional SWE (2D-SWE) to examine the vessels around the plaques. The potential links with the degree of stenosis, plaque type, and cardiovascular risk were analyzed. Results: In the RA group, the 2D-SWE values showed significant positive correlations with the severity of the atherosclerotic plaques (rs = 0.461; 95% CI: 0.049 to 0.739; p = 0.023) and the degree of stenosis (rs = 0.920; 95% CI: 0.793 to 0.970; p < 0.001). Based on 2D-SWE, a ROC curve analysis distinguished higher severity plaques from lower severity plaques with an AUC = 0.818, 95% CI: 0.683 to 0.913. The optimal cut-off value of 2D-SWE > 32.40 kPa was associated with a sensitivity of 96%, a specificity of 56%, a positive predictive value (PPV) of 66.70%, and a negative predictive value (NPV) of 92.90%. Conclusion: Elastography can be an effective technique for assessing and stratifying atherosclerotic plaques in patients with RA, as well as for aiding in the early detection and subsequent prevention of future complications. [ABSTRACT FROM AUTHOR]

Objective: Blood lipid levels play a critical role in the progression of atherosclerosis. However, even with adequate lipid reduction, significant residual cardiovascular risk remains. Therefore, it is necessary to seek novel therapeutic strategies for atherosclerosis that can not only lower lipid levels but also inhibit inflammation simultaneously. Methods: The fusion protein FD03-IL-1Ra was designed by linking the Angiopoietin-like 3 (ANGPTL3) nanobody and human interleukin-1 receptor antagonist (IL-1Ra) sequences to a mutated human immunoglobulin gamma 1 (IgG1) Fc. This construct was transfected into HEK293 cells for expression. The purity and thermal stability of the fusion protein were assessed using SDS-PAGE, SEC-HPLC, and differential scanning calorimetry. Binding affinities of the fusion protein to ANGPTL3 and IL-1 receptor were measured using Biacore T200. The biological activity of the fusion protein was validated through in vitro experiments. The therapeutic efficacy of the fusion protein was evaluated in an ApoE-/- mouse model of atherosclerosis, including serum lipid level determination, histological analysis of aorta and aortic sinus sections, and detection of inflammatory and oxidative stress markers. ImageJ software was utilized for quantitative image analysis. Statistical analysis was performed using one-way ANOVA followed by Bonferroni post hoc test. Results: The FD03-IL-1Ra fusion protein was successfully expressed, with no polymer formation detected, and it demonstrated good thermal and conformational stability. High affinity for both murine and human ANGPTL3 was exhibited by FD03-IL-1Ra, and it was able to antagonize hANGPTL3's inhibition of LPL activity. FD03-IL-1Ra also showed high affinity for both murine and human IL-1R, inhibiting IL-6 expression in A549 cells induced by IL-1β stimulation, as well as suppressing IL-1β-induced activity inhibition in A375.S2 cells. Our study revealed that the fusion protein effectively lowered serum lipid levels and alleviated inflammatory responses in mice. Furthermore, the fusion protein enhanced plaque stability by increasing collagen content within atherosclerotic plaques. Conclusions: These findings highlighted the potential of bifunctional interleukin-1 receptor antagonist and ANGPTL3 antibody fusion proteins for ameliorating the progression of atherosclerosis, presenting a promising novel therapeutic approach targeting both inflammation and lipid levels. [ABSTRACT FROM AUTHOR]

Introduction: There are sex differences in the extent, severity, and outcomes of coronary artery disease. We aimed to assess the influence of sex on coronary atherosclerotic plaque activity measured using coronary 18F-sodium fluoride (18F-NaF) positron emission tomography (PET), and to determine whether 18F-NaF PET has prognostic value in both women and men. Methods: In a post-hoc analysis of observational cohort studies of patients with coronary atherosclerosis who had undergone 18F-NaF PET CT angiography, we compared the coronary microcalcification activity (CMA) in women and men. Results: Baseline 18F-NaF PET CT angiography was available in 999 participants (151 (15%) women) with 4282 patient-years of follow-up. Compared to men, women had lower coronary calcium scores (116 [interquartile range, 27–434] versus 205 [51–571] Agatston units; p = 0.002) and CMA values (0.0 [0.0-1.12] versus 0.53 [0.0-2.54], p = 0.01). Following matching for plaque burden by coronary calcium scores and clinical comorbidities, there was no sex-related difference in CMA values (0.0 [0.0-1.12] versus 0.0 [0.0-1.23], p = 0.21) and similar proportions of women and men had no 18F-NaF uptake (53.0% (n = 80) and 48.3% (n = 73); p = 0.42), or CMA values > 1.56 (21.8% (n = 33) and 21.8% (n = 33); p = 1.00). Over a median follow-up of 4.5 [4.0–6.0] years, myocardial infarction occurred in 6.6% of women (n = 10) and 7.8% of men (n = 66). Coronary microcalcification activity greater than 0 was associated with a similarly increased risk of myocardial infarction in both women (HR: 3.83; 95% CI:1.10-18.49; p = 0.04) and men (HR: 5.29; 95% CI:2.28–12.28; p < 0.001). Conclusion: Although men present with more coronary atherosclerotic plaque than women, increased plaque activity is a strong predictor of future myocardial infarction regardless of sex. [ABSTRACT FROM AUTHOR]

Objective: To explore the clinical value of computed tomography (CT) liver-to-spleen (L/S) attenuation ratio in patients with non-alcoholic fatty liver disease (NAFLD) accompanied by atherosclerotic plaque (AP). Methods: This was a single-center, retrospective, observational study of patients who were diagnosed with NAFLD undergoing CT scans at Beijing Changping Hospital of Chinese Medicine from April 2020 to April 2022. Patients were grouped according to whether they had a diagnosis of AP or not. Healthy individuals without NAFLD undergoing CT scans during the same period were also included as a control group. The patients were matched for gender, age, and BMI in a 1:1:1 ratio. Correlations between the CT L/S attenuation ratio, liver function indicators, and blood lipid levels were assessed in the three groups. The predictive value of the CT L/S attenuation ratio was evaluated using the receiver operating characteristic (ROC) curve and the area under the curve (AUC) analyses. Results: Eighty-nine cases in each group. The three groups had significant differences in liver function and blood lipid levels (P<0.05). The CT L/S attenuation ratio in the NAFLD+AP and NAFLD groups was lower than that in the control group and was the lowest in the NAFLD+AP group (P<0.05). There was no significant correlation between the CT L/S attenuation ratio and liver function indicators (P>0.05), but it positively correlated with high-density lipoprotein (HDL) and negatively correlated with low-density lipoprotein (LDL), triglycerides (TG), and total cholesterol (TC) (P<0.05). The CT L/S attenuation ratio had a high predictive value for NAFLD patients with AP (AUC=0.859). Conclusions: The CT L/S attenuation ratio in NAFLD patients with AP is significantly reduced and is closely related to the levels of blood lipid indicators. The CT L/S attenuation ratio has a high predictive value for NAFLD patients with AP. [ABSTRACT FROM AUTHOR]

Lipid-associated macrophages (LAMs) occur in a broad range of diseased structures and lesions in tissues important for metabolic homeostasis. LAMs can be distinguished from other tissue-resident macrophages by their lipid-handling capacity and expression of specific marker genes (e.g., Trem2 , Gpnmb , and CD36). LAMs exhibit a functional spectrum (with respect to inflammation, lipid handling, and efferocytosis) that can vary depending on metabolic and disease state, location, and microenvironmental needs. LAM pools emerge largely from monocyte-derived precursors, but may also increase in abundance through (re-)polarization and self-renewal. Evidence for the importance of LAMs in metabolic disease justifies ventures into therapeutics that manipulate LAM abundance and phenotypes. Lipid-associated macrophages (LAMs) are phagocytic cells with lipid-handling capacity identified in various metabolic derangements. During disease development, they locate to atherosclerotic plaques, adipose tissue (AT) of individuals with obesity, liver lesions in steatosis and steatohepatitis, and the intestinal lamina propria. LAMs can also emerge in the metabolically demanding microenvironment of certain tumors. In this review, we discuss major questions regarding LAM recruitment, differentiation, and self-renewal, and, ultimately, their acute and chronic functional impact on the development of metabolic diseases. Further studies need to clarify whether and under which circumstances LAMs drive disease progression or resolution and how their phenotype can be modulated to ameliorate metabolic disorders. [ABSTRACT FROM AUTHOR]

• Advances in single-cell biology have revolutionized the understanding of atherosclerosis, highlighting the interaction between different cell populations and molecular pathways in plaque progression and regression. • The formation and progression of atherosclerotic plaques are driven by LDL cholesterol and chronic exposure to pro-inflammatory stimuli, resulting in endothelial dysfunction and the formation of foam cells. • The concept of "vulnerable plaque" describes plaques prone to rupture, erosion, or calcified nodules, leading to acute coronary syndrome (ACS). Modern imaging techniques like IVUS, NIRS, and OCT are crucial for identifying and assessing these high-risk plaques. • Intensive lipid-lowering therapies, particularly statins and PCSK9 inhibitors, have shown efficacy in reducing plaque volume and stabilizing plaque features, with ongoing research needed to confirm their long-term benefits in reducing cardiovascular events. Atherosclerotic cardiovascular disease (ASCVD) remains a leading cause of death globally despite advances in preventive therapies. Understanding of the initiation and progression of atherosclerosis, the interplay between lipoproteins, endothelial dysfunction, inflammation, and immune responses is critical to treating this disease. The development of vulnerable coronary plaques prone to thrombosis, can lead to acute coronary syndromes, for these reasons, the potential plaque stabilization and regression through pharmacological interventions, particularly lipid-lowering agents like statins and PCSK9 inhibitors is crucial. The imaging techniques such as intravascular ultrasound (IVUS), near-infrared spectroscopy (NIRS), and optical coherence tomography (OCT) play a key role in assessing plaque composition and guiding interventional therapeutic strategies. Clinical evidence supports the efficacy of intensive lipid-lowering therapy in inducing plaque regression, with studies demonstrating reductions in plaque volume and improvements in plaque morphology assessed by IVUS, OCT and NIRS. While pharmacological interventions show promise in promoting plaque regression and stabilization, their impact on long-term cardiovascular events requires further investigation. Multimodality imaging and comprehensive outcome trials are proposed as essential tools for elucidating the relationship between plaque modification and clinical benefit in coronary atherosclerosis. The stabilization or regression of atherosclerotic plaque might serve as the phenomenon linking the reduction in LDL-C levels to the decrease in cardiovascular events. Overall, this review emphasizes the ongoing efforts to advance our understanding of ASCVD pathophysiology and optimize therapeutic approaches for improving patient outcomes. [Display omitted] [ABSTRACT FROM AUTHOR]

• Collagen type VIII is a non-fibrillar, short-chain, network-forming collagen expressed throughout the vasculature. • Collagen VIII is dysregulated in cardiovascular, lung, and renal diseases, as well as in certain cancers. • Collagen VIII plays active roles in angiogenesis, vessel compliance and repair, and atherosclerosis. • Collagen VIII modulates pathways involved in extracellular matrix remodeling. Collagens have dual functions in the extracellular matrix (ECM), acting as both structural components and signaling molecules in matricellular communication. Although collagen molecules share a common triple helix motif, the supramolecular organization helps classify them into nearly 30 different types of collagens. Collagen type VIII is a non-fibrillar, short-chain, network-forming collagen that is expressed throughout the vasculature. Collagen VIII expression is aberrant in cardiovascular, lung, and renal disease, as well as in several different types of cancer. It plays active roles in angiogenesis, vessel injury repair, maintenance of arterial compliance, atherosclerotic plaque formation and stability modulation, fibrosis, and ECM remodeling. This review presents an overview of the characteristics of collagen VIII in vascular-related disorders, from clinical significance to laboratory studies, with a major focus on highlighting the signaling properties of collagen VIII in the vascular ECM. The expression patterns of collagen VIII in human diseases and experimental animal models highlight the protein's important yet underexplored functions. A deeper understanding of its mechanisms and downstream signaling pathways may pave the way for translational and tissue engineering applications of collagen VIII. [ABSTRACT FROM AUTHOR]

Understanding the viscoelastic properties of atherosclerotic plaques at rupture-prone scales is crucial for assessing their vulnerability. Here, we develop a Hybrid Hierarchical theory-Microrheology (HHM) approach, enabling the analysis of multiscale mechanical variations and distribution changes in regional tissue viscoelasticity within plaques across different spatial scales. We disclose a universal two-stage power-law rheology in plaques, characterized by distinct power-law exponents (α short and α long), which serve as mechanical indexes for plaque components and assessing mechanical gradients. We further propose a self-similar hierarchical theory that effectively delineates plaque heterogeneity from the cytoplasm, cell, to tissue levels. Moreover, our proposed multi-layer perceptron model addresses the viscoelastic heterogeneity and gradients within plaques, offering a promising diagnostic strategy for identifying unstable plaques. These findings not only advance our understanding of plaque mechanics but also pave the way for innovative diagnostic approaches in cardiovascular disease management. Our study pioneers a Hybrid Hierarchical theory-Microrheology (HHM) approach to dissect the intricate viscoelasticity of atherosclerotic plaques, focusing on distinct components including cap fibrosis, lipid pools, and intimal fibrosis. We unveil a universal two-stage power-law rheology capturing mechanical variations across plaque structures. The proposed hierarchical model adeptly captures viscoelasticity changes from cytoplasm, cell to tissue levels. Based on the newly proposed markers, we further develop a machine learning (ML) diagnostic model that sets precise criteria for evaluating plaque components and heterogeneity. This work not only reveals the comprehensive mechanical heterogeneity within plaques but also introduces a mechanical marker-based ML strategy for assessing plaque conditions, offering a significant leap towards understanding and diagnosing atherosclerotic risks. [Display omitted] [ABSTRACT FROM AUTHOR]

Atherosclerotic cardiovascular disease remains a major health issue, often developing silently as subclinical atherosclerotic disease (SAD). The Mediterranean diet (MDiet) is known for its cardiovascular benefits, but the combined influence of both MDiet adherence and physical activity (PA) on SAD progression has not been previously documented. Objective: We aimed to investigate how adherence to a healthy lifestyle, defined as MDiet adherence and PA level, influences SAD progression in subjects from the ILERVAS cohort follow-up. Methods: A study on 3097 participants from the ILERVAS prospective cohort was conducted. MDiet adherence was assessed using the MEDAS score, and PA categories were established using the IPAQ, both categorized into low, moderate, and high levels. Two different lifestyle scores integrating the MDiet and PA categories were built. The presence of atherosclerotic plaques was assessed by carotid and femoral ultrasound examination. Demographic, clinical, and biochemical data were also obtained. Multivariable linear, logistic, and Poisson regression models adjusted for potential confounders were used to analyze the association between the lifestyle scores and SAD progression, as well as the MDiet and PA as separate variables and number of territories with plaque. Results: A healthier lifestyle score did not show an effect on SAD progression. However, a higher MEDAS score was associated with a 3% decrease in the number of territories with plaque (IRR 0.97, 95% CI 0.96–0.99, p < 0.001), suggesting a protective effect of the adherence to the MDiet. PA did not show a significant association (IRR 1.00, 95% CI 1.00–1.00, p = 0.269). Older age, hypertension, dyslipidemia, smoking, and lower eGFR were associated with SAD progression, while the female sex was protective (IRR 0.67, 95% CI 0.63–0.72, p < 0.001). Conclusions: The findings of this study show that higher adherence to the MDiet is associated with reduced incidence of SAD, indicating its potential role in cardiovascular prevention strategies. Although a higher lifestyle score or physical activity levels did not show any significant effect, promoting the MDiet, alongside managing traditional cardiovascular risk factors, could be an effective public health intervention to prevent atherosclerosis and reduce the burden of cardiovascular disease. [ABSTRACT FROM AUTHOR]

Objective: The aim of this work was to study the relationship between carotid atherosclerosis (CAS) and several indexes and provide a basis for the prevention and treatment of cardiovascular and cerebrovascular diseases. Methods: There were 11,028 adults who underwent physical examination at the Guangzhou Cadre and Talent Health Management Center from January 2023 to December 2023 and were selected as research subjects. Retrospective analysis was used to understand the carotid atherosclerosis of the examined population and analyze its relationship with sex, age, blood pressure, blood glucose, blood lipids, renal function, 25-hydroxyvitamin D, neutrophil to lymphocyte count ratio (NLR), platelet to lymphocyte count ratio (PLR), systemic immune inflammation index (SII), monocyte count to high-density lipoprotein cholesterol ratio (MHR), triglyceride glucose body mass index (TyG-BMI), insulin resistance metabolic index (METS-IR), and other indicators. Results: Among 11,028 subjects, the detection rate of carotid atherosclerotic thickening (CAT) was 12.00% and carotid atherosclerotic plaque (CAP) was 25.11%. The CAT and CAP detection rates in men were 13.32% and 28.78%, respectively, which were higher than the CAT detection rate of 8.28% and CAP detection rate of 14.80% in women, and the differences were statistically significant (both p < 0.001). Multivariate logistic regression analysis using TyG-BMI and METS-IR as two indicators was modeled separately, and the results showed that CAS was associated with men, increasing age, and systolic blood pressure. The area under the curve (AUC) was analyzed using the subject's work characteristic (ROC) curve in the descending order of METS-IR, TyG-BMI, and MHR. The combination of the three indexes of sex, age, and METS-IR predicted atherosclerosis with the highest AUC values. Conclusion: Carotid atherosclerosis is highly prevalent in men. Elevation of systolic blood pressure, fasting glucose, MHR, and TyG-BMI (or METS-IR) with age are independent influences on carotid atherosclerosis. The three indexes of MHR, TyG-BMI, and METS-IR, respectively, in combination with sex and age, can be used as a new and effective index to predict CAS. [ABSTRACT FROM AUTHOR]

Incretin receptor agonists (IRAs), primarily composed of glucagon-like peptide-1 receptor agonists (GLP-1RAs) and glucose-dependent insulinotropic polypeptide receptor agonists (GIPRAs), work by mimicking the actions of the endogenous incretin hormones in the body. GLP-1RAs have been approved for use as monotherapy and in combination with GIPRAs for the management of type 2 diabetes mellitus (T2DM). In addition to their role in glucose regulation, IRAs have demonstrated various benefits such as cardiovascular protection, obesity management, and regulation of bone turnover. Some studies have suggested that IRAs not only aid in glycemic control but also exhibit anti-atherosclerotic effects. These agents have been shown to modulate lipid abnormalities, reduce blood pressure, and preserve the structural and functional integrity of the endothelium. Furthermore, IRAs have the ability to mitigate inflammation by inhibiting macrophage activation and promoting M2 polarization. Research has also indicated that IRAs can decrease macrophage foam cell formation and prevent vascular smooth muscle cell (VSMC) phenotype switching, which are pivotal in atheromatous plaque formation and stability. This review offers a comprehensive overview of the protective effects of IRAs in atherosclerotic disease, with a focus on their impact on atherogenesis. [ABSTRACT FROM AUTHOR]

Background: Few prospective studies explored the incidence and determinant of carotid atherosclerosis (CA) progression (CAP). This community-based prospective study focused on the effects of diabetes mellitus (DM) treatments and glucose levels on CAP risks. Methods: We followed up a group of 657 CA-positive middle-aged adults and elders for CAP. CAP was defined as an increase in the total number of carotid plaque and/or an increase in diameter stenosis by at least 10%. Results: After 4.05 years of followed-up, CAP was detected in 364 (55.4%) subjects. The multivariable-adjusted hazard ratios (HRs) were 1.805 (95% confidence interval [CI]: 1.374-2.358) and 0.694 (95% CI: 0.510-0.944) for elevated fasting plasma glucose (eFPG; FPG≥100 mg/dL) and glucose-lowering medications (GLM), respectively. As compared to GLM-negative+eFPG-positive subjects, the multivariable-adjusted HRs were 0.497 (95% CI: 0.373-0.662), 0.537 (95% CI: 0.306-0.942), and 0.586 (95% CI: 0.412-0.833) for GLM-negative +eFPG-negative, GLM-positive+eFPG-negative, and GLM-positive+ eFPG-positive subjects, respectively. The multivariable-adjusted risks of CAP were similar between GLM-negative+eFPG-negative and GLM-positive+ eFPG-positive subjects (p=0.77). Stratified analyses showed that the multivariable-adjusted HRs per 5.0 mg/dL increase in FPG were significantly increased among GLM-negative subjects (HR=1.131; 95% CI: 1.094-1.171) and non)significantly decreased among GLM-positive subjects (HR=0.985; 95% CI: 0.957-1.013). Conclusion: We found that more than 50% of CA-positive subjects had CAP in 4 years and higher FPG significantly increased and GLM significantly decreased the risks of CAP. Additionally, GLM and FPG demonstrated an interactive effect on CAP risks. It seems possible that GLM may induce effects beyond lowering glucose levels and subsequently lowers CAP risks. [ABSTRACT FROM AUTHOR]

Atherosclerosis serves as the primary catalyst for numerous cardiovascular diseases. Growing evidence suggests that the immune response is involved in every stage of atherosclerotic plaque evolution. Rapid, but not specific, innate immune arms, including neutrophils, monocytes/macrophages, dendritic cells (DCs) and other innate immune cells, as well as pattern-recognition receptors and various inflammatory mediators, contribute to atherogenesis. The specific adaptive immune response, governed by T cells and B cells, antibodies, and immunomodulatory cytokines potently regulates disease activity and progression. In the inflammatory microenvironment, the heterogeneity of leukocyte subpopulations plays a very important regulatory role in plaque evolution. With advances in experimental techniques, the fine mechanisms of immune system involvement in atherosclerotic plaque evolution are becoming known. In this review, we examine the critical immune responses involved in atherosclerotic plaque evolution, in particular, looking at atherosclerosis from the perspective of evolutionary immunobiology. A comprehensive understanding of the interplay between plaque evolution and plaque immunity provides clues for strategically combating atherosclerosis. [ABSTRACT FROM AUTHOR]

Recently, cellular senescence-induced unstable carotid plaques have gained increasing attention. In this study, we utilized bioinformatics and machine learning methods to investigate the correlation between cellular senescence and the pathological mechanisms of unstable carotid plaques. Our aim was to elucidate the causes of unstable carotid plaque progression and identify new therapeutic strategies. First, differential expression analysis was performed on the test set GSE43292 to identify differentially expressed genes (DEGs) between the unstable plaque group and the control group. These DEGs were intersected with cellular senescence-associated genes to obtain 40 cellular senescence-associated DEGs. Subsequently, key genes were then identified through weighted gene co-expression network analysis, random forest, Recursive Feature Elimination for Support Vector Machines algorithm and cytoHubba plugin. The intersection yielded 3 CSA-signature genes, which were validated in the external validation set GSE163154. Additionally, we assessed the relationship between these CSA-signature genes and the immune landscape of the unstable plaque group. This study suggests that cellular senescence may play an important role in the progression mechanism of unstable plaques and is closely related to the influence of the immune microenvironment. Our research lays the foundation for studying the progression mechanism of unstable carotid plaques and provides some reference for targeted therapy. [ABSTRACT FROM AUTHOR]

Background: The hypothesis that not only diagnosed diabetes (DM), but also milder dysglycemia may affect the development of atherosclerosis still requires further study. In our population-based study, we aimed to evaluate the impact of prediabetic state on preclinical atherosclerosis and whether it may affect the cardiovascular risk (CVR) in the general population. Methods: The analysis was a part of the Bialystok PLUS cohort study and represented a random sample of Bialystok (Poland) residents aged 20–79 years at the time of sampling (July 2017-January 2023). The cross-sectional analysis included 1431 participants of a population-based study (mean age 46.82 years). Comprehensive biochemical assessments were performed. An Oral Glucose Tolerance Test (OGTT) was performed on fasting patients who did not report having a DM. Results: The population with prediabetes, based on HbA1c and OGTT, accounted for more than half of the study participants (n = 797, 55.7%). Atherosclerotic plaques in the carotid arteries were significantly more common in individuals with prediabetes considering all CVR categories. Prediabetes was associated with the occurrence of more advanced preclinical atherosclerosis, especially in the low to moderate CVR category. Serum glucose concentration after 1h and HbA1c proved to be statistically significant indicators of the presence of atherosclerotic plaques in ultrasound (respectively, AUC = 0.73 and 0.72). In multivariate logistic regression, prediabetes was independently associated with significantly increased risk of preclinical atherosclerosis (OR = 1.56, 95% CI 1.09–2.24), along with CVR categories, pulse wave velocity and central blood pressure augmentation index. Conclusions: Prediabetes is associated with the occurrence and progression of the preclinical atherosclerosis. Importantly, many of those patients are in the low to moderate cardiovascular risk category, hence may have a severely underestimated risk. Inclusion of prediabetes into CVR assessment may improve risk stratification. An early identification of dysglycemic population is necessary to effectively implement the cardiovascular and metabolic prevention measures. [ABSTRACT FROM AUTHOR]

Atherosclerosis is an age‐related pathological process associated with elevated levels of legumain in plaques and plasma. However, the underlying mechanisms remain unclear. The aim of this study was to investigate the role of legumain in the progression of atherosclerotic plaques, with a particular focus on functional and phenotypic changes in CD4+ T cells. Apolipoprotein E‐deficient (Apoe−/−) mice were crossed with legumain‐deficient (Lgmn−/−) mice to generate Lgmn−/−Apoe−/− mice. CD4+ T cells accumulated in the atherosclerotic plaques of Apoe−/− mice fed a high‐fat diet. Deletion of legumain attenuated the deposition of CD4+ T cells in plaques and reduced the number of atherosclerotic lesions. The levels of CD4+ T cells in the blood, lymph nodes, and spleen were decreased in Lgmn−/− mice. Transcriptomic analysis revealed that the deletion of legumain decreased the differentiation, survival, and function of CD4+ memory T cells by suppressing the T cell receptor (TCR) signaling pathway. These changes are accompanied by the downregulation of the antiapoptotic protein B‐cell lymphoma 2 (Bcl‐2) and the reduced release of interleukin (IL)‐2 and interferon (IFN)‐γ. These results suggest that legumain deficiency may play a role in the development of atherosclerosis by impairing the survival, proliferation, and function of CD4+ T cells. Inhibition of legumain activity may be an innovative therapy for the treatment of atherosclerosis. [ABSTRACT FROM AUTHOR]

Current diagnostic technique in direct identification of multi‐site plaques and simultaneous assessment of plaque vulnerability remains a challenge, which is crucial for indicating the risk of atherosclerotic cardiovascular diseases (ASCVD). Herein, an osteopontin (OPN)‐specific nanoprobe (OPN Ab‐Au/FeNiPO4@ICG) with both multiple spectra optoacoustic tomography (MSOT) and computed tomography (CT) imaging, is constructed successfully realizing systemic screening of vulnerable plaque. OPN Ab‐Au/FeNiPO4@ICG nanoprobe specifically targeted OPN‐overexpressed foam cells and recognized the vulnerable plaque at the molecular level. In AS mice, CT imaging exhibits that OPN Ab‐Au/FeNiPO4@ICG nanoprobe effectively avoid interference from calcification and accurately visualized AS plaque. MSOT functional imaging results reveals that after the injection of OPN Ab‐Au/FeNiPO4@ICG nanoprobe, the carotid plaque exhibited a much higher MSOT signal than the aortic arch plaque (P = 0.0291). Further pathological analysis displays that the carotid plaque possessed a much higher vulnerability score (P = 0.0247), in agreement with the MSOT signals. More importantly, the linear regression analysis confirms the high correlation between the MSOT signals and plaque vulnerability with R = 0.7095 (P = 0.0216), demonstrating the potential of the proposed nanoprobe in systematic evaluation of plaque vulnerability. This work employs the dual‐model nanoprobe strategy for both plaque localization and vulnerability assessment, greatly advancing the accurate diagnosis of ASCVD. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to investigate the risk factors affecting the presence of carotid plaque in asymptomatic adults. Methods: Asymptomatic adults (age > 40 years, no symptoms of cardiovascular and cerebrovascular diseases) undergoing routine health examinations from physical examination department were included in this study. Carotid plaque was measured by Resona 7OB and Resona 8EXP color Doppler ultrasound and L9-3U and L4-5WU probes. The focal carotid intima–media thickness was greater than 1.1 mm, and the local protrusion of the artery wall into the artery lumen suggested the presence of carotid atherosclerotic plaque. According to their ultrasound results, 1077 asymptomatic adults were divided into a group with carotid plaque (477) and a group without carotid plaque (600). Results: A total of 1077 asymptomatic adults were included in this study, of whom 44.3% had carotid plaque. The proportion of men with carotid plaque was 84.5%. Multifactorial logistic analysis suggested that age, fasting blood glucose (FBG), total cholesterol (TC), homocysteine (Hcy) and male gender were risk factors for carotid atherosclerosis. The predictive probability of these risk factor indicators derived from the multifactorial model was calculated using receiver operating characteristic (ROC) curves with SPSS 25.0 software. The calculated area under the receiver operating characteristic curve (AUC) was 0.715 (95% CI, 0.685–0.746). Conclusion: Age, FBG, TC, Hcy and male gender are risk factors for carotid atherosclerosis in asymptomatic adults. Gender differences in carotid atherosclerosis deserve further attention. [ABSTRACT FROM AUTHOR]

Background: In mouse models of atherosclerosis, knockout of the PLA2G2A gene has been shown to reduce the volume of atherosclerotic plaques. Clinical trials have demonstrated the potential of using the sPLA2 inhibitor Varespladib in combination with statins to reduce lipid levels. However, this approach has not yielded the expected results in reducing the risk of cardiovascular events. Therefore, it is necessary to further investigate the mechanisms of PLA2G2A. Methods: Single-cell transcriptome data from two sets of carotid plaques, combined with clinical patient information. were used to describe the expression characteristics of PLA2G2A in carotid plaques at different stages. In order to explore the mechanisms of PLA2G2A, we conducted enrichment analysis, cell–cell communication analysis and single-cell regulatory network inference and clustering analyses. We validated the above findings at the cellular level. Results: Our findings indicate that PLA2G2A is primarily expressed in vascular fibroblasts and shows significant cell interactions with macrophages in the early-stage, especially in complement and inflammation-related pathways. We also found that serum sPLA2 levels have stronger diagnostic value in patients with mild carotid artery stenosis. Subsequent comparisons of single-cell transcriptomic data from early and late-stage carotid artery plaques corroborated these findings and predicted transcription factors that might regulate the progression of early carotid atherosclerosis (CA) and the expression of PLA2G2A. Conclusions: Our study discovered and validated that PLA2G2A is highly expressed by vascular fibroblasts and promotes plaque progression through the activation of macrophage complement and coagulation cascade pathways in the early-stage of CA. [ABSTRACT FROM AUTHOR]

Objective: This research is aimed at unravelling the intricate relationship between transient receptor potential vanilloid 6 (TRPV6), protein kinase A (PKA), uncoupling protein 2 (UCP2), and atherosclerosis. By shedding light on the role of the TRPV6/PKA/UCP2 pathway in inhibiting inflammatory response and cell apoptosis in coronary atherosclerotic plaques, this study provides valuable insights into potential therapeutic targets for treating coronary artery disease (CAD). Methods: We established animal and cell models of atherosclerosis. The expression of TRPV6 was measured using immunohistochemistry and immunofluorescence. Cytokine levels were detected by enzyme‐linked immunosorbent assay (ELISA). Cell viability and apoptosis ratio were measured using cell counting kit‐8 (CCK‐8) and flow cytometry. The binding relationship between TRPV6 and PKA was validated using chromatin immunoprecipitation (CHIP) and coimmunoprecipitation (CoIP). Finally, the expression of the TRPV6/PKA/UCP2 signaling pathway and apoptosis‐related factors was detected using western blot (WB) and quantitative real‐time polymerase chain reaction (qRT‐PCR). Results: TRPV6 was significantly decreased in atherosclerosis mouse and cell model. CHIP and CoIP assays indicated that TRPV6 binds to PKA and positively regulated its expression in oxidized low‐density lipoprotein (ox‐LDL)–treated human umbilical vein endothelial cells (HUVECs). Overexpression of TRPV6 significantly increased cell viability and inhibited apoptosis, whereas silencing TRPV6 had the opposite effect. Additionally, the overexpression of TRPV6 remarkably declined the expression of tumor necrosis factor‐alpha (TNF‐α), interleukin‐6 (IL‐6), and interleukin‐1 beta (IL‐1β). However, after silencing PKA, this effect was partially reversed, the cell viability and inflammatory response remarkably enhanced, and apoptosis significantly declined in oe‐TRPV6 + si‐PKA group. Conclusions: In summary, our study demonstrated that TRPV6 inhibited apoptosis and inflammatory response in the atherosclerosis cell model through the regulation of the PKA/UCP2 pathway. [ABSTRACT FROM AUTHOR]

Introduction: Atherosclerosis (AS) is considered the underlying cause of many diseases, particularly cardiovascular and cerebrovascular diseases. Inulin, a type of fructan, has shown potential in improving atherosclerosis, although there are conflicting findings. It is hypothesized that the polymerization degree of inulin may largely influence its therapeutic effectiveness. Therefore, this study aimed to investigate the effects and mechanisms of short-chain and long-chain inulin in AS. Methods: ApoE−/− mice fed a high fat diet (HFD) were used to establish an atherosclerosis model. These mice received daily oral administration of either short-chain or long-chain inulin for 12 weeks. Plasma lipid metabolism-related indices were measured using biochemical analysis, and plasma immunological indices were analyzed via ELISA. The aorta, aortic root regions, liver tissue, adipose tissue, and colon tissue were examined through various staining techniques, including ORO staining, hematoxylin and eosin staining, Alcian blue staining, and immunofluorescent or immunohistochemical assays. Microbiome analysis was conducted in the cecal content. Results: The results indicated that both short-chain and long-chain inulin substantially reduced the formation of atherosclerotic plaques. Inulin also improved plasma lipid concentrations and hepatic lipid metabolism, and partially alleviated both localized (atherosclerotic lesions) and systemic inflammation. Short-chain inulin was more effective than long-chain inulin in reducing atherosclerotic plaques formation, enhancing lipid metabolism and reducing inflammation. Additionally, both types of inulin showed similar effectiveness in enhancing intestinal epithelial barrier integrity, gut microbiota composition and functionality. Conclusion: These findings suggest that inulin has a protective role against atherosclerosis by enhancing lipid metabolism, reducing inflammation, and improving intestinal barrier and gut microbiota. As a dietary intervention, shortchain inulin is more effective than long-chain inulin, offering clinical implications for using inulin as a therapeutic agent for atherosclerosis. [ABSTRACT FROM AUTHOR]

Background: Chronic kidney disease (CKD) is a significant public health concern associated with a high prevalence of carotid plaques, which are indicators of atherosclerosis and predictors of adverse cardiovascular outcomes. Inflammation is a hallmark of CKD, contributing to both renal dysfunction and cardiovascular complications. This study aims to investigate the association between inflammatory markers—systemic inflammatory response index (SIRI), systemic immune-inflammation index (SII), aggregate inflammatory status index (AISI), monocyte to high-density lipoprotein cholesterol ratio (MHR), neutrophil to high-density lipoprotein cholesterol ratio (NHR), neutrophil to lymphocyte ratio (NLR), and monocyte to lymphocyte ratio (MLR)—and carotid plaques in CKD patients, and to explore the potential mediating role of estimated glomerular filtration rate (eGFR) in this relationship. Methods: A cross-sectional analysis was conducted on patients admitted to the Division of Nephrology between January 2023 and June 2023. The primary endpoint was the presence of carotid plaques assessed using ultrasound imaging. Multivariable logistic regression models were used to examine the associations between inflammatory markers and carotid plaques, and trend tests were performed to evaluate the trending association of carotid plaques risk and inflammatory markers in tertiles. Restricted cubic spline (RCS) analysis was used to assess potential non-linear relationships, and subgroup analyses were conducted to examine consistency across different strata. Mediation analysis was performed to explore the role of eGFR. Results: Of the 609 participants, 387 were included in the final analysis after applying exclusion criteria. Elevated levels of LnSIRI (OR = 1.87, 95% CI = 1.25–2.80), LnSII (OR = 1.67, 95% CI = 1.09–2.56), LnAISI (OR = 1.70, 95% CI = 1.22–2.37), LnMHR (OR = 1.94, 95% CI = 1.15–3.26), LnNHR (OR = 1.82, 95% CI = 1.10–3.02), and LnMLR (OR = 2.26, 95% CI = 1.18–4.34) were significantly associated with the presence of carotid plaques. There were significant trends for increasing tertiles of SIRI, AISI, MHR and NHR. RCS analysis showed no significant non-linear associations. Subgroup analyses indicated similar associations across most strata. eGFR partially mediated these relationships, with proportions mediated ranging from 14.7 to 17.5%. Conclusions: Inflammatory markers are significantly associated with carotid plaques in CKD patients, with eGFR playing a partial mediating role. These findings highlighted the importance of managing inflammation and maintaining renal function to mitigate the risk of atherosclerosis in CKD patients. Trial registration: Not applicable. [ABSTRACT FROM AUTHOR]

Introduction: Carotid artery stenting is an alternative interventional treatment to carotid endarterectomy. However, preprocedural considerations and anatomical risk factor analyses for carotid artery stenting are currently insufficient. Therefore, we investigated the high-risk anatomical appearance of carotid artery stenting from the neurointerventionist perspective to predict periprocedural complications. Materials and methods: We retrospectively reviewed patients with carotid stenosis who underwent carotid artery stenting at a comprehensive stroke center between January 2012 and December 2021. We compared the demographic characteristics, medical history, and anatomical appearance of the stenotic segment in patients with and without complications. Results: We analyzed a total of 148 patients (64 women [43.2%]; median age, 73.0 [interquartile range, 65.5-79.0]). Complications occurred in 39 of the 148 patients, primarily minor and transient. Of baseline or procedural characteristics, a high initial National Institutes of Health Stroke Scale score (p = 0.04), symptomatic stenosis (p = 0.01), and curve-centered plaque of the proximal ICA (p = 0.01) were significantly associated with carotid artery stenting complications in unadjusted analysis. Curve-centered plaque remained an independent risk factor for carotid artery stenting complications after adjustment (odds ratio 2.23[1.02-4.88], p = 0.04). Conclusion: High-risk vascular anatomical features, such as curve-centered plaque, are associated with a high frequency of periprocedural complications of carotid artery stenting. Tailored patient selection for carotid stenosis is crucial to prevent complications. Patients with curve-centered plaque should consider alternative treatment options such as carotid endarterectomy to achieve optimal clinical results. [ABSTRACT FROM AUTHOR]

Monocytes directly contribute to atherosclerosis development by their recruitment to plaques in which they differentiate into macrophages. In the present study, we ask how modulating monocyte glucose metabolism could affect their homeostasis and their impact on atherosclerosis. Here we investigate how circulating metabolites control monocyte behavior in blood, bone marrow and peripheral tissues of mice. We find that serum glucose concentrations correlate with monocyte numbers. In diet-restricted mice, monocytes fail to metabolically reprogram from glycolysis to fatty acid oxidation, leading to reduced monocyte numbers in the blood. Mechanistically, Glut1-dependent glucose metabolism helps maintain CD115 membrane expression on monocytes and their progenitors, and regulates monocyte migratory capacity by modulating CCR2 expression. Results from genetic models and pharmacological inhibitors further depict the relative contribution of different metabolic pathways to the regulation of CD115 and CCR2 expression. Meanwhile, Glut1 inhibition does not impact atherosclerotic plaque development in mouse models despite dramatically reducing blood monocyte numbers, potentially due to the remaining monocytes having increased migratory capacity. Together, these data emphasize the role of glucose uptake and intracellular glucose metabolism in controlling monocyte homeostasis and functions. Monocytes participate in plaque formation, and adapt to metabolic changes to alter their functions. Here the authors show, using genetic mouse models and functional analyses, that Glut1-mediated glucose metabolism is important for regulating monocyte homeostasis and migration, but curiously has no impact on atherosclerotic plaque formation. [ABSTRACT FROM AUTHOR]

In vulnerable atherosclerotic plaques, intraplaque hemorrhages (IPH) result in hemolysis of red blood cells and release of hemoglobin and free hemin. Hemin activates platelets and leads to thrombosis. Agonism of the inhibitory platelet receptor ACKR3 inhibits hemin‐dependent platelet activation and thrombus formation. To characterize the effect of hemin and ACKR3 agonism on isolated human platelets, multi‐color flow cytometry and classical experimental setup such as light transmission aggregometry and a flow chamber assay were used. Hemin induces platelet aggregation and ex vivo platelet‐dependent thrombus formation on immobilized collagen under a low shear rate of 500 s−1, indicating that free hemin is a strong activator of platelet‐dependent thrombosis. Recently, we described that ACKR3 is a prominent inhibitory receptor of platelet activation. Specific ACKR3 agonists but not conventional antiplatelet compounds such as COX‐1 inhibitor (indometacin), ADP‐receptor blocker (cangrelor), or PAR1 inhibitor (ML161) inhibit both hemin‐dependent aggregation and thrombus formation. To further characterize the effect of hemin on platelet subpopulations, we established a multi‐color flow cytometry assay. We found that hemin induces procoagulant (CD42bpos/PAC‐1neg/AnnexinVpos), aggregatory (CD42bpos/PAC‐1pos/AnnexinVneg), and inflammatory (CD42bpos/CXCR4pos/ACKR3pos/AnnexinVpos) platelet subpopulations. Treatment with ACKR3 agonists significantly decreased the formation of procoagulant and ACKR3pos platelets in response to hemin. We conclude that hemin is a strong activator for the formation of procoagulant platelets and thrombus formation which is dependent on the function of ACKR3. Activation of ACKR3 using specific agonists may offer a therapeutic strategy to regulate the vulnerability of atherosclerotic plaques in areas of IPH. [ABSTRACT FROM AUTHOR]

Background Results Conclusion Maintaining low concentrations of plasma low‐density lipoprotein cholesterol (LDLc) over time decreases the number of LDL particles trapped within the artery wall, slows the progression of atherosclerosis and delays the age at which mature atherosclerotic plaques develop. This substantially reduces the lifetime risk of atherosclerotic cardiovascular disease (ASCVD) events. In this context, plaque development and vulnerability result not only from lipid accumulation but also from inflammation.Changes in the composition of immune cells, including macrophages, dendritic cells, T cells, B cells, mast cells and neutrophils, along with altered cytokine and chemokine release, disrupt the equilibrium between inflammation and anti‐inflammatory mechanisms at plaque sites. Considering that it is not a competition between LDLc and inflammation, but instead that they are partners in crime, the present narrative review aims to give an overview of the main inflammatory molecular pathways linked to raised LDLc concentrations and to describe the impact of lipid‐lowering approaches on the inflammatory and lipid burden. Although remarkable changes in LDLc are driven by the most recent lipid lowering combinations, the relative reduction in plasma C‐reactive protein appears to be independent of the magnitude of LDLc lowering.Identifying clinical biomarkers of inflammation (e.g. interleukin‐6) and possible targets for therapy holds promise for monitoring and reducing the ASCVD burden in suitable patients. [ABSTRACT FROM AUTHOR]

Atherosclerosis is a dynamic process. There is little evidence regarding whether quantification of atherosclerosis extent and progression, particularly in the carotid artery, in asymptomatic individuals predicts all-cause mortality. This study sought to evaluate the independent predictive value (beyond cardiovascular risk factors) of subclinical atherosclerosis burden and progression and all-cause mortality. A population of 5,716 asymptomatic U.S. adults (mean age 68.9 years, 56.7% female) enrolled between 2008 and 2009 in the BioImage (A Clinical Study of Burden of Atherosclerotic Disease in an At Risk Population) study underwent examination by vascular ultrasound to quantify carotid plaque burden (cPB) (the sum of right and left carotid plaque areas) and by computed tomography for coronary artery calcium (CAC). Follow-up carotid vascular ultrasound was performed on 732 participants a median of 8.9 years after the baseline exam. All participants were followed up for all-cause mortality, the primary outcome. Trend HRs are the per-tertile increase in each variable. Over a median 12.4 years' follow-up, 901 (16%) participants died. After adjustment for cardiovascular risk factors and background medication, baseline cPB and CAC score were both significantly associated with all-cause mortality (fully adjusted trend HR: 1.23; 95% CI: 1.16-1.32; and HR: 1.15; 95% CI: 1.08-1.23), respectively (both P < 0.001), thus providing additional prognostic value. cPB performed better than CAC score. In participants with a second vascular ultrasound evaluation, median cPB progressed from 29.2 to 91.3 mm3. cPB progression was significantly associated with all-cause mortality after adjusting for cardiovascular risk factors and baseline cPB (HR: 1.03; 95% CI: 1.01-1.04 per absolute 10-mm3 change; P = 0.01). Subclinical atherosclerosis burden (cPB and CAC) in asymptomatic individuals was independently associated with all-cause mortality. Moreover, atherosclerosis progression was independently associated with all-cause mortality. [ABSTRACT FROM AUTHOR]

Emerging evidence indicates that chemical exposures in the environment are overlooked drivers of cardiovascular diseases (CVD). Recent evidence suggests that micro- and nanoplastic (MNP) particles derived largely from the chemical or mechanical degradation of plastics might represent a novel CVD risk factor. Experimental data in preclinical models suggest that MNPs can foster oxidative stress, platelet aggregation, cell senescence, and inflammatory responses in endothelial and immune cells while promoting a range of cardiovascular and metabolic alterations that can lead to disease and premature death. In humans, MNPs derived from various plastics, including polyethylene and polyvinylchloride, have been detected in atherosclerotic plaques and other cardiovascular tissues, including pericardia, epicardial adipose tissues, pericardial adipose tissues, myocardia, and left atrial appendages. MNPs have measurable levels within thrombi and seem to accumulate preferentially within areas of vascular lesions. Their presence within carotid plaques is associated with subsequent increased incidence of cardiovascular events. To further investigate the possible causal role of MNPs in CVD, future studies should focus on large, prospective cohorts assessing the exposure of individuals to plastic-related pollution, the possible routes of absorption, the existence of a putative safety limit, the correspondence between exposure and accumulation in tissues, the timing between accumulation and CVD development, and the pathophysiological mechanisms instigated by pertinent concentrations of MNPs. Data from such studies would allow the design of preventive, or even therapeutic, strategies. Meanwhile, existing evidence suggests that reducing plastic production and use will produce benefits for the environment and for human health. This goal could be achieved through the UN Global Plastics Treaty that is currently in negotiation. [ABSTRACT FROM AUTHOR]

Background: Investigation into the immune heterogeneity linked with atherosclerosis remains understudied. This knowledge gap hinders the creation of a robust theoretical framework essential for devising personalized immunotherapies aimed at combating this disease. Methods: Single-cell RNA sequencing (scRNA-seq) analysis was employed to delineate the immune cell-type landscape within atherosclerotic plaques, followed by assessments of cell-cell interactions and phenotype characteristics using scRNA-seq datasets. Subsequently, pseudotime trajectory analysis was utilized to elucidate the heterogeneity in cell fate and differentiation among macrophages. Through integrated approaches, including single-cell sequencing, Weighted Gene Co-expression Network Analysis (WGCNA), and machine learning techniques, we identified hallmark genes. A risk score model and a corresponding nomogram were developed and validated using these genes, confirmed through Receiver Operating Characteristic (ROC) curve analysis. Additionally, enrichment and immune characteristic analyses were conducted based on the risk score model. The model's applicability was further corroborated by in vitro and in vivo validation of specific genes implicated in atherosclerosis. Result: This comprehensive scRNA-seq analysis has shed new light on the intricate immune landscape and the role of macrophages in atherosclerotic plaques. The presence of diverse immune cell populations, with a particularly enriched macrophage population, was highlighted by the results. Macrophage heterogeneity was intricately characterized, revealing four distinct subtypes with varying functional attributes that underscore their complex roles in atherosclerotic pathology. Intercellular communication analysis revealed robust macrophage interactions with multiple cell types and detailed pathways differing between proximal adjacent and atherosclerotic core groups. Furthermore, pseudotime trajectories charted the developmental course of macrophage subpopulations, offering insights into their differentiation fates within the plaque microenvironment. The use of machine learning identified potential diagnostic markers, culminating in the identification of RNASE1 and CD14. The risk score model based on these biomarkers exhibited high accuracy in diagnosing atherosclerosis. Immune characteristic analysis validated the risk score model's efficacy in defining patient profiles, distinguishing high-risk individuals with pronounced immune cell activities. Finally, experimental validation affirmed RNASE1's involvement in atherosclerotic progression, suggesting its potential as a therapeutic target. Conclusion: Our findings have advanced our understanding of atherosclerosis immunopathology and paved the way for novel diagnostic and therapeutic strategies. [ABSTRACT FROM AUTHOR]

Objectives: The long-term durability of carotid artery stenting (CAS) may be determined by various factors; however, residual stenosis is a known risk factor for in-stent restenosis. The authors of this article utilized cone-beam computed tomography (CBCT) in angiosuite to investigate plaque features affecting the character and quality of stent expansion after CAS. Methods: Forty-two CAS cases with both pre- and post-CAS CBCT evaluations were included in this retrospective analysis. Five features derived from pre-CAS images were tested: (1) eccentricity, (2) overballoon, (3) maximum plaque thickness, (4) calcification barrier, and (5) stenotic degree. For post-CAS CBCT, stent configuration was assessed if the stent was expanded and oval or round in shape as well as outward or inward in orientation. Variables were tested if they were associated with oval expansion, outward expansion, and 20% residual stenosis after CAS. Results: Oval or outward expansion is directly related to residual stenosis. The oval expansion was associated with maximum plaque thickness, and outward expansion was associated with the presence of a calcification barrier. Variables related to > 20% residual stenosis were the maximum plaque thickness, calcification barrier, and pre-CAS stenotic degree. Conclusions: CBCT for carotid stenosis may provide valuable information about plaque features, especially calcification features that may interfere with the angioplasty effect, as well as the characteristics and quality of stent expansion. Residual stenosis > 20% was associated with calcification barrier, maximum plaque thickness, and pre-CAS stenotic degree. [ABSTRACT FROM AUTHOR]

Introduction Transplant vasculopathy resembles atherosclerotic plaque formation and is a major contributor to late graft failure in kidney transplant recipients (KTR). Remnant lipoproteins and associated triglycerides are causal risk factors for atherosclerotic plaques and have been implicated in late kidney graft failure. However, whether remnants derived from liver (containing apolipoprotein [apo] B100) or intestine (containing apoB48) are clinically more important is unclear. The current study investigated the association between baseline fasting apoB48 levels and late kidney graft failure. Methods 481 KTR with a functioning graft for at least 1 year were included in this retrospective, observational longitudinal single center cohort study. The primary endpoint was death-censored late graft failure, defined as need for initiation of dialysis or re-transplantation. ApoB48 was measured by enzyme-linked immunosorbent assay. Results During a median follow-up of 9.5 years, 61 KTR developed graft failure (12.7%). At baseline, KTR with higher apoB48 levels had lower eGFR (P < .001), lower high-density lipoprotein (HDL) cholesterol (P < .001), increased triglycerides (P < .001) and used cyclosporine more frequently (P = .003). Cox regression showed that higher baseline apoB48 was associated with higher risk of late graft failure [hazard ratio (95% confidence interval), 1.59 (1.22, 2.07), P < .001], independent of stepwise adjustment for potential confounders, including age and sex, immunosuppression type and proteinuria, triglycerides, and waist circumference (fully adjusted HR, 1.78 (1.29, 2.47), P < .001]. Conclusion ApoB48 is strongly associated with late graft failure, independent of potential confounders. Since apoB48-containing lipoproteins originate from the intestine, this study provides a rationale for considering pharmacological interventions targeting lipid absorption to improve graft outcome. [ABSTRACT FROM AUTHOR]

Cardiovascular disease (CVD) is a group of conditions involving the heart or blood vessels and is a leading cause of death and disability worldwide. Carotid artery plaque, as a key risk factor, is crucial for the early prevention and management of CVD. The purpose of this study is to combine clinical application and deep learning techniques to design a predictive model for the carotid artery plaque area. This model aims to identify individuals at high risk and reduce the incidence of cardiovascular disease through the implementation of relevant preventive measures. This study proposes an innovative multi-gate attention capture (MGAC) model that utilizes data such as risk factors, laboratory tests, and physical examinations to predict the area of carotid artery plaque. Experimental findings reveal the superior performance of the MGAC model, surpassing other commonly used deep learning models with the following metrics: mean absolute error of 4.17, root mean square error of 10.89, mean logarithmic squared error of 0.21, and coefficient of determination of 0.98. [ABSTRACT FROM AUTHOR]

Introduction: Carotid atherosclerotic plaques with neovascularisation pose a high risk of rupture, leading to ischemic stroke. Contrast-enhanced ultrasound (CEUS) is a novel technique for evaluating neovascularisation in these plaques, but its quantitative application in assessing drug efficacy remains limited. This study aimed to quantitatively analyse the curative effect of atorvastatin on carotid plaques using the CEUS time-intensity curve. Materials and methods: A total of 95 cases of carotid plaques were randomly divided into experimental and control groups, and the subjects underwent one year of follow-up observation. CEUS time-intensity curve analysis was used to monitor contrast agent perfusion and quantify contrast images. Results: The study group showed significantly lower intima media thickness (IMT) values after 12 months than the control group (P < 0.05). The IMT value of the study group after 12 months of treatment was significantly lower than before treatment, and the difference was statistically significant (P < 0.05). A statistically significant difference in enhancement intensity (EI) values between the two groups was observed both after 6 months and 12 months of treatment (P < 0.05); the research group was significantly lower than the control group. Furthermore, EI values were significantly lower in the study group after 6 and 12 months of treatment (P < 0.05). Conclusion: In conclusion, CEUS and time-intensity curve analysis can be used to assess drug effects (atorvastatin) intervention in treating unstable carotid plaques. [ABSTRACT FROM AUTHOR]

Background: The monocyte–lymphocyte ratio (MLR) is a hematological test parameter that reflects the status of both monocytes and lymphocytes as inflammatory cells. This study aims to investigate the relationship between MLR and carotid intraplaque neovascularization (IPN) in patients with asymptomatic carotid stenosis. Methods: We performed the Angio Planewave Ultrasensitive (AngioPLUS) screening for patients with carotid plaques. The carotid plaque stability was evaluated by semiquantitative visual grading of carotid IPN. Binary logistic regression models were performed to determine the associations between different clinical and laboratory indicators and the presence of high IPN. Results: A total of 160 patients were eventually enrolled with 99 in the low IPN group (Scores 0–1) and 61 in the high IPN group (Score 2). Univariate logistic regression showed that age, monocytes, lymphocytes, glycated hemoglobin (HbA1c), fibrinogen, d‐dimmer, and MLR were significantly associated with the presence of high IPN (all p < 0.05). Multivariate logistic regression models showed that MLR was significantly associated with the presence of high IPN after adjusting for other covariates. An MLR value of 32.9 was the optimal cutoff value to differentiate high and low IPN. High MLR was also significantly correlated with the presence of high IPN (odds ratio [OR] = 4.08, 95% confidence interval [CI]: 1.69–9.88, p = 0.002) when included in the above multivariate logistic regression model. Conclusion: Elevated MLR is closely associated with the presence of high IPN and may serve as a surrogate biomarker for carotid IPN. [ABSTRACT FROM AUTHOR]

Background: Proprotein convertase subtilisin/kexin type 9 (PCSK9) is primarily recognized for its role in lipid metabolism, but recent evidence suggests that it may have broader implications due to its diverse tissue expression. Objective: This review aims to explore the multifaceted functions of PCSK9, highlighting its pro‐atherosclerotic effects, including its impact on circulating lipoprotein variables, non‐low‐density lipoprotein receptors, and various cell types involved in atherosclerotic plaque development. Conclusions: PCSK9 exhibits diverse roles beyond lipid metabolism, potentially contributing to atherosclerosis through multiple pathways. Understanding these mechanisms could offer new insights into therapeutic strategies targeting PCSK9 for cardiovascular disease management. [ABSTRACT FROM AUTHOR]

Background: Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors have emerged as a novel class of drugs with cardioprotective effects through their lipid‐lowering effects. Objective: This review aims to discuss existing and novel strategies of PCSK9 inhibition, providing an overview of established randomized controlled trials and ongoing outcome trials that assess the efficacy and long‐term safety of PCSK9 inhibitors. It also explores the evolving role of PCSK9 beyond lipid metabolism and outlines the pleiotropic actions of PCSK9 inhibition in various disorders and future directions including novel strategies to target PCSK9. Conclusion: PCSK9 inhibition shows promise not only in lipid metabolism but also in other disease processes, including atherosclerotic plaque remodeling, acute coronary syndrome, stroke, inflammation, and immune response. [ABSTRACT FROM AUTHOR]

To develop and validate a clinical-radiomics nomogram for predicting early ischemic stroke risk in patients who sustain a transient ischemic attack (TIA). A retrospective training dataset (n = 76) and a prospective validation dataset (n = 34) of patients with TIA were studied. Image processing was performed using ITK-snap and Artificial Intelligent Kit. Radiomics features were selected in R. A nomogram predicting recurrent TIA/stroke in 90 days as a recurrent ischemic event was established. Model performance was assessed by computing the receiver operating characteristic curve and decision curve analysis (DCA). We found a higher proportion of diabetes and hypertension in the patients with recurrent TIA compared with the stable patients in both the training and validation datasets (P < 0.05). Recurrent patients had significantly higher ABCD2 scores and plaque scores compared to stable patients. ABCD2 score and necrotic/lipid core area were independent risk factors for recurrent ischemic events (odds ratio [OR], 2.75; 95% confidence interval [CI], 1.47–6.40; and OR, 1.20; 95% CI, 1.07–1.41, respectively). The radiomics model had area under the curve values of 0.737 (95% CI, 0.715–0.878) in the training dataset and 0.899 (95% CI, 0.706–0.936) in the validation dataset, which was superior to the ABCD2 score and plaque model for predicting stroke recurrence (P < 0.05). The nomogram predicting recurrent ischemic events was 0.923 (95% CI, 0.895–0.978) in the training dataset and 0.935 (95% CI, 0.830–0.959) in the validation dataset. DCA confirmed the clinical value of this nomogram. The nomogram, based on clinical ABCD2 score, carotid plaque components and radiomics score, shows good performance in predicting the risk of recurrent ischemic events in patients with TIA. [ABSTRACT FROM AUTHOR]

The editorial delves into the process of extracellular calcification in the human body, emphasizing its significance in skeletal development, defense against infections, and repair of damaged arteries. It presents a bell-shaped curve distribution of calcification strength in the population, indicating that a robust calcification process may be linked to improved survival and infection defense. The text also explores the impact of calcification on bone density, osteoporosis, osteoarthritis, and cardiovascular diseases, underscoring the importance of studying this process for a holistic understanding of health and disease. The authors advocate for further research in various fields to enhance knowledge on calcification and its implications on human health. [Extracted from the article]

Background/Objectives: Cerebrovascular events, such as strokes, are often preceded by the rupture of atherosclerotic plaques in the carotid arteries. This work introduces a novel approach to predict the occurrence of such events by integrating computational fluid dynamics (CFD), structural analysis, and machine learning (ML) techniques. The objective is to develop a predictive model that combines both imaging and non-imaging data to assess the risk of carotid atherosclerosis and subsequent cerebrovascular events, ultimately improving clinical decision-making. Methods: A multidisciplinary approach was employed, utilizing 3D reconstruction techniques and blood-flow simulations to extract key plaque characteristics. These were combined with patient-specific clinical data for risk evaluation. The study involved 134 asymptomatic individuals diagnosed with carotid artery disease. Data imbalance was addressed using two distinct approaches, with the optimal method chosen for training a Gradient Boosting Tree (GBT) classifier. The model's performance was evaluated in terms of accuracy, sensitivity, specificity, and ROC AUC. Results: The best-performing GBT model achieved a balanced accuracy of 88%, with a ROC AUC of 0.92, a sensitivity of 0.88, and a specificity of 0.91. This demonstrates the model's high predictive power in identifying patients at risk for cerebrovascular events. Conclusions: The proposed method effectively combines CFD, structural analysis, and ML to predict cerebrovascular event risk in patients with carotid artery disease. By providing clinicians with a tool for better risk assessment, this approach has the potential to significantly enhance clinical decision-making and patient outcomes. [ABSTRACT FROM AUTHOR]