Search

Members of the Bacteroidota compose a large portion of the human gut microbiota, contributing to overall gut health via the degradation of various polysaccharides. This process is facilitated by lipoproteins, globular proteins anchored to the cell surface by a lipidated N-terminal cysteine. Despite their importance, lipoprotein synthesis by these bacteria is understudied. In Escherichia coli, the a-amino- linked lipid of lipoproteins is added by the lipoprotein N-acyltransferase Lnt. Herein, we have identified a protein distinct from Lnt responsible for the same process in Bacteroides, named lipoprotein N-acyltransferase in Bacteroides (Lnb). Deletion of Lnb yields cells that synthesize diacylated lipoproteins, with impacts on cell viability and morphology, growth on polysaccharides, and protein composition of membranes and outer membrane vesicles (OMVs). Our results not only challenge the accepted paradigms of lipoprotein biosynthesis in gram-negative bacteria but also suggest the existence of a new family of lipoprotein N-acyltransferases. [ABSTRACT FROM AUTHOR]

Identifying biomarkers for Alzheimer's disease (AD) is crucial, due to its complex pathology, which involves dysfunction in lipid transport, contributing to neuroinflammation, synaptic loss, and impaired amyloid-β clearance. Nuclear magnetic resonance (NMR) is able to quantify and stratify lipoproteins. The study investigated lipoproteins in blood from AD patients, aiming to evaluate their diagnostic potential. Serum and plasma were collected from AD patients (n = 25) and healthy individuals (n = 25). We conducted a comprehensive lipoprotein profiling on serum samples using NMR spectroscopy, analysing 112 lipoprotein subfractions. In plasma, we measured unspecific markers of neuronal damage and AD hallmark proteins using single molecule array technology. Additionally, clinical data and cerebrospinal fluid biomarker levels were also collected to enrich our data. Our findings, after adjusting for age and sex differences, highlight significant alterations in two specific lipoproteins; high-density lipoprotein (HDL)-1 Apo-A2 (H1A2) and HDL-2 Apo-A2 (H2A2), both with area under the curve (AUC) values of 0.67, 95% confidence interval (CI) = 0.52–0.82). These results indicate that these lipoprotein subfractions may have potential as indicators of AD-related metabolic changes. [ABSTRACT FROM AUTHOR]

Inflammation and oxidative stress are the key factors in the pathogenesis of both metabolic dysfunction‐associated steatohepatitis (MASH) and atherosclerosis. Obeticholic acid (OCA), a farnesoid X receptor (FXR) agonist, improves hepatic inflammation and fibrosis in patients with MASH. However, it also reduces HDL cholesterol, suggesting that OCA may increase cardiovascular disease (CVD) risk in patients with MASH. We assessed HDL cholesterol efflux function, antioxidant (paraoxonase and ceruloplasmin activity), pro‐inflammatory index, and particle sizes in a small group of patients with and without diabetes (n = 10/group) at baseline and after 18 months of OCA treatment. Patients on lipid‐lowering medications (statins, fibrates) were excluded. At baseline, ferritin levels were higher in patients with MASH without diabetes (336.5 [157.0, 451.0] vs. 83 [36.0, 151.0] ng/mL, p < 0.005). Markers of HDL functions were similar in both groups. OCA therapy significantly improved liver histology and liver enzymes but increased alkaline phosphatase levels in nondiabetic patients with MASH (p < 0.05). However, it did not have any significant effect on cholesterol efflux and the antioxidant paraoxonase functions. In nondiabetics, ceruloplasmin (CP) antioxidant activity decreased (p < 0.005) and the pro‐inflammatory index of HDL increased (p < 0.005) due to OCA therapy. In contrast, in diabetics, OCA increased levels of pre‐β‐HDL—the HDL particles enhanced protective capacity (p = 0.005) with no alteration in HDL functionality. In all patients, serum glucose levels were negatively correlated with OCA‐induced change in pro‐inflammatory function in HDL (p < 0.001), which was primarily due to diabetes (p = 0.05). These preliminary results suggest a distinct effect of OCA therapy on diabetic and nondiabetic patients with MASH and warrant a future large‐scale study. [ABSTRACT FROM AUTHOR]

Lipoproteins and apolipoproteins are crucial in lipid metabolism, functioning as essential mediators in the transport of cholesterol and triglycerides and being closely related to the pathogenesis of multiple systems, including cardiovascular. Lipoproteins a (Lp(a)), as a unique subclass of lipoproteins, is a low-density lipoprotein(LDL)-like particle with pro-atherosclerotic and pro-inflammatory properties, displaying high heritability. More and more strong evidence points to a possible link between high amounts of Lp(a) and cardiac conditions like atherosclerotic cardiovascular disease (ASCVD) and aortic stenosis (AS), making it a risk factor for heart diseases. In recent years, Lp(a)'s role in other diseases, including neurological disorders and cancer, has been increasingly recognized. Although therapies aimed at low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) have achieved significant success, elevated Lp(a) levels remain a significant clinical management problem. Despite the limited efficacy of current lipid-lowering therapies, major clinical advances in new Lp(a)-lowering therapies have significantly advanced the field. This review, grounded in the pathophysiology of lipoproteins, seeks to summarize the wide-ranging connections between lipoproteins (such as LDL-C and HDL-C) and various diseases, alongside the latest clinical developments, special emphasis is placed on the pivotal role of Lp(a) in cardiovascular disease, while also examining its future potential and mechanisms in other conditions. Furthermore, this review discusses Lp(a)-lowering therapies and highlights significant recent advances in emerging treatments, advocates for further exploration into Lp(a)'s pathogenic mechanisms and its potential as a therapeutic target, proposing new secondary prevention strategies for high-risk individuals. [ABSTRACT FROM AUTHOR]

Dyslipidemia is an important risk factor for cardiovascular morbidity and mortality. Although low-density lipoprotein (LDL) is primarily responsible, the importance of triglyceride (TG) and high-density lipoprotein (HDL) has also been recognized. The present study investigated the effect of the atherogenic index of plasma (AIP), in which atherogenic and protective lipoproteins were evaluated together, on the initial flow in patients with ST elevation myocardial infarction. AIP was calculated as log(TG/HDL-cholesterol). Patients included in the study (n = 1535) were divided into Thrombolysis in Myocardial Infarction (TIMI) flow grade 0 and >0. AIP was found to be significantly different between 2 groups (.55 ±.23 vs.67 ±.21; P <.001). AIP was an independent predictor for pre-intervention TIMI flow (Odds Ratio: 2.778). A moderate correlation was found between TIMI frame count measurements, calculated in patients with TIMI 2–3, and AIP (Pearson correlation coefficient:.63, P <.001). In the receiver operating characteristic analysis, AIP showed the highest area under curve (AUC) compared with other lipid parameters for predicting vascular patency. The AUC of AIP was.634, the cut-off value was.59, and the sensitivity and specificity were 67.6% and 68.4%, respectively (P <.001). In conclusion, AIP was found to be an important marker affecting pre-percutaneous coronary intervention TIMI flow. [ABSTRACT FROM AUTHOR]

Extracellular vesicles (EVs) are mediators of intercellular communication, recently recognised for their clinical applications. Accurate characterisation and quantification of EVs are critical for understanding of their function and clinical relevance. Many platforms utilise fluorescence for EV characterisation, frequently labelling surface proteins to identify EVs. The heterogeneity of EVs and the lack of a universal protein marker encourages the use of generic EV labelling methods, including membrane labelling. Using nano‐flow cytometry, we evaluated six membrane dyes, including MemGlow and CellMask. Evaluation criteria included EV labelling efficacy, non‐specific labelling of very low‐density lipoproteins (VLDLs), brightness and dye aggregation. Significant variation was observed in dye performance, with certain dyes showing poor EV labelling efficacy or high affinity to VLDLs. Importantly, several promising candidates were identified for further investigation. Overall, this study highlights the importance of selecting appropriate membrane dyes for EV staining tailored to the aims of the study and the EV origin. MemGlow and CellMask proved favourable, allowing bright, sensitive staining of EV membranes with minimal aggregation. However, MemGlow showed an affinity to VLDLs, and CellMask requires additional sample handling for optimal labelling. These results contribute to deepening our understanding of EV membrane dyes, allowing for better dye selection and EV identification in future studies. [ABSTRACT FROM AUTHOR]

Background: Evidence-based screening is crucial to detect myocardial ischemia in high-risk diabetics. We explored the relationship between nitric oxide (NO) levels, lipid profile indices, and atherogenic index of plasma (AIP) in type 2 diabetics with coronary artery disease (CAD) and to determine their potential as prognostic markers. Materials and Methods: A case--control study included 50 diabetics with CAD (cases), 30 diabetics without CAD (control 1), and 23 healthy controls (control 2). Biochemical parameters were determined using standard protocols; plasma NO was measured via the Griess reaction. Results: Cases had the highest levels of NO, fasting blood sugar, glycated hemoglobin (HbA1c), and triglycerides, and the lowest total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) levels. Cases exhibited the highest TC: HDL-C, LDL-C: HDL-C, and AIP ratios. A significant positive correlation between NO and HbA1c (r = 0.328, P = 0.020). Conclusion: Chronic hyperglycemia could enhance NO overproduction driven by inducible isoform, suggesting a potential role for chronic hyperglycemia in endothelial dysfunction and vascular complications in diabetes. [ABSTRACT FROM AUTHOR]

Homozygous familial hypercholesterolemia (HoFH), is a rare genetic disorder characterized by dual mutations in the low-density lipoprotein receptor (LDLR) gene, leading to dysfunctional or absent LDLRs, often accompanied by severe premature Atherosclerotic Cardiovascular Disease (ASCVD) and exhibiting refractoriness to aggressive pharmacological interventions. Double filtration plasmapheresis (DFPP), a form of lipoprotein apheresis (LA), has been effectively utilized as an adjunctive treatment modality to reduce serum LDL-C levels in refractory cases of HoFH. Here, we report a case of a 36-year-old female with HoFH who developed xanthomas on her limbs and waist at age 7. Despite maximum-tolerated doses of statins from age 32, combined with ezetimibe and evolocumab, her LDL-C levels remained critically elevated at 12–14 mmol/L. Her genetic testing confirmed a homozygous LDLR mutation. At 35 years old, she experienced exertional chest pain, and percutaneous coronary intervention revealed severe calcific left main stenosis, necessitating stent implantation. Subsequently, she initiated once every 1–2 months DFPP. Pre-DFPP, her LDL-C and total cholesterol (TC) levels were 13.82 ± 3.28 and 15.45 ± 0.78 mmol/L, respectively. Post-DFPP, her LDL-C and TC levels significantly decreased to 2.43 ± 0.33 mmol/L (81.76 ± 4.11% reduction) and 3.59 ± 0.41 mmol/L (76.76 ± 2.75% reduction), respectively. Lipoprotein (a) and triglycerides also decreased by 89.10 ± 1.39% and 42.29 ± 15.68%,respectively. Two years later, there was no progression of coronary artery disease, and her symptoms and xanthomas regressed significantly. Collectively, DFPP effectively reduces LDL-C levels in refractory cases of HoFH and contributes to delaying ASCVD progression, representing an efficacious adjunctive therapeutic modality. [ABSTRACT FROM AUTHOR]

Objectives Cardiovascular disease through accelerated atherosclerosis is a leading cause of mortality for patients with systemic lupus erythematosus (SLE), likely due to increased chronic inflammation and cardiometabolic defects over age. We investigated age-associated changes in metabolomic profiles of SLE patients and healthy controls (HCs). Methods Serum NMR metabolomic profiles from female SLE patients (n  = 164, age = 14–76) and HCs (n  = 123, age = 13–72) were assessed across age by linear regression and by age group between patients/HCs (Group 1, age ≤ 25, n  = 62/46; Group 2, age = 26–49, n  = 50/46; Group 3, age ≥ 50, n  = 52/31) using multiple t tests. The impact of inflammation, disease activity and treatments were assessed, and UK Biobank disease-wide association analysis of metabolites was performed. Results Age-specific metabolomic profiles were identified in SLE patients vs HCs, including reduced amino acids (Group 1), increased very-low-density lipoproteins (Group 2), and increased low-density lipoproteins (Group 3). Twenty-five metabolites were significantly altered in all SLE age groups, dominated by decreased atheroprotective high-density lipoprotein (HDL) subsets, HDL-bound apolipoprotein (Apo)A1 and increased glycoprotein acetyls (GlycA). Furthermore, ApoA1 and GlycA were differentially associated with disease activity and serological measures, as well as atherosclerosis incidence and myocardial infarction mortality risk through disease-wide association. Separately, glycolysis pathway metabolites (acetone/citrate/creatinine/glycerol/lactate/pyruvate) uniquely increased with age in SLE, significantly influenced by prednisolone (increased pyruvate/lactate) and hydroxychloroquine (decreased citrate/creatinine) treatment and associated with type 1 and type 2 diabetes by disease-wide association. Conclusions Increasing HDL (ApoA1) levels through therapeutic/nutritional intervention, whilst maintaining low disease activity, in SLE patients from a young age could improve cardiometabolic disease outcomes. Biomarkers from the glycolytic pathway could indicate adverse metabolic effects of current therapies. [ABSTRACT FROM AUTHOR]

Background:: Liver plays a vital role in lipid metabolism. It contributes both in exogenous and endogenous cycles of lipid metabolism and transport of lipids through plasma. Liver disease impacts on hepatic synthesis of lipoproteins and lipogenesis but data on dyslipidemia during disease progression are limited. Aims & Objectives: To assess the serum Lipid profile in patients diagnosed with chronic alcoholic liver disease (ALD) in a tertiary care level hospital and to assess the association of Serum Lipid profile alterations with the severity of alcoholic liver disease. Materials & Methods: The present study was conducted in the Department of Medicine, Dr Panjabrao Alias Bhausaheb Deshmukh Memorial Medical College and Research Centre, Amravati on 73 patients with chronic alcoholic liver disease and >18 years of age of both sex. Then they were subjected to Clinical data, including demographic information, medical history, liver function tests, imaging findings. Serum Lipid Profile Levels including triglycerides, cholesterol, and lipoproteins were measured using standardized laboratory assays, with values expressed in mg/dL. Disease severity was assessed using established scoring systems such as Child-Pugh classification. Results: Mean S Cholesterol levels was 192±43.67 mg/dl,S triglyceride was 136.9±87.23 mg/dl,HDL was 31.4±11.76 mg/dl,LDL was 92.58±32.64 mg/dl and VLDL was 27.54±14.12 mg/dl. One way Anova was applied which states that the S Cholesterol, Triglyceride and HDL had statistical significant difference among 3 groups with p value <0.05. Conclusion: The severity of Chronic alcoholic Liver Disease increases from Child pugh score class A to Child pugh score class C, the lipid panel profile decreases exponentially. [ABSTRACT FROM AUTHOR]

Background: Glaucoma is a leading cause of vision impairment and permanent blindness. Primary open-angle glaucoma (POAG) is a prominent type of primary glaucoma; however, its cause is difficult to determine. This study aimed to analyze the serum lipid profile of Chinese POAG patients and assess its correlation with intraocular pressure (IOP). Methods: The study included 1,139, 1,248, and 356 Chinese individuals with POAG, primary angle closure glaucoma (PACG), and controls, respectively. Peripheral whole blood samples were collected at the time of diagnosis. Enzymatic colorimetry was used to determine serum levels of different lipids: high-density lipoproteins (HDL), low-density lipoproteins (LDL), triglycerides, cholesterol, and very low-density lipoproteins (VLDL). Additionally, immunoturbidimetry was used to quantify serum levels of apolipoproteins A (APOA), B (APOB), E (APOE), and lipoprotein A [Lp(a)], while intraocular pressure (IOP) was measured in all patients with POAG. Results: After adjusting for age and sex, patients with POAG exhibited elevated serum levels of VLDL, APOA, and APOE but mitigated cholesterol levels compared with the control participants. Significantly lower serum triglyceride, VLDL, and Lp(a) levels were found in patients with PACG than in control participants. Serum cholesterol (P = 0.019; β = -0.75, 95% confidence interval [CI]: -1.38 – -0.12) and HDL levels (P < 0.001; β = -2.91, 95% CI: -4.58 – -1.25) were inversely linked to IOP in patients with POAG, after adjusting for age, sex, and ocular metrics. In addition, serum Lp(a) levels were correlated with the average IOP (P = 0.023; β = -0.0039, 95% CI: -0.0073 – -0.006) and night peak (P = 0.027; β = -0.0061, 95% CI: -0.0113 – -0.0008) in patients with POAG. Conclusions: Significantly different serum lipid and lipoprotein profiles were observed in POAG and PACG patients. This study highlighted the differences in serum lipid and lipoprotein levels among Chinese POAG patients and their relationship with IOP and IOP fluctuation. Serum lipid and lipoprotein profiles should be considered while evaluating glaucoma risk. [ABSTRACT FROM AUTHOR]

Background: Retention of apolipoprotein B (apoB)-containing lipoproteins within the arterial wall plays a major causal role in atherosclerotic cardiovascular disease (ASCVD). There is a single apoB molecule in all apoB-containing lipoproteins. Therefore, quantitation of apoB directly estimates the number of atherogenic particles in plasma. ApoB is the preferred measurement to refine the estimate of ASCVD risk. Low-density lipoprotein (LDL) particles are by far the most abundant apoB-containing particles. In patients with elevated lipoprotein(a) (Lp(a)), apoB may considerably underestimate risk because Mendelian randomization studies have shown that the atherogenicity of Lp(a) is approximately 7-fold greater than that of LDL on a per apoB particle basis. In subjects with increased Lp(a), the association between LDL-cholesterol and incident CHD (coronary heart disease) is increased, but the association between apoB and incident CHD is diminished or even lost. Thus, there is a need to understand the mechanisms of Lp(a), LDL-cholesterol and apoB-related CHD risk and to provide clinicians with a simple practical tool to address these complex and variable relationships. How can we understand a patient's overall lipid-driven atherogenic risk? What proportion of this risk does apoB capture? What proportion of this risk do Lp(a) particles carry? To answer these questions, we created a novel metric of atherogenic risk: risk-weighted apolipoprotein B. Methods: In nmol/L: Risk-weighted apoB = apoB - Lp(a) + Lp(a) x 7 = apoB + Lp(a) x 6. Proportion of risk captured by apoB = apoB divided by risk-weighted apoB. Proportion of risk carried by Lp(a) = Lp(a) × 7 divided by risk-weighted apoB. Results: Risk-weighted apoB agrees with risk estimation from large epidemiological studies and from several Mendelian randomization studies. Conclusions: ApoB considerably underestimates risk in individuals with high Lp(a) levels. The association between apoB and incident CHD is diminished or even lost. These phenomena can be overcome and explained by risk-weighted apoB. [ABSTRACT FROM AUTHOR]

Simple Summary: Pulmonary surfactant prevents alveolar collapse by reducing surface tension at the air–liquid interface. It contains two hydrophilic lectins, called SP-A and SP-D. They are factors of innate immune defence but also contribute to the surfactant structure and homeostasis. SP-A and SP-D recognise pathogen- or danger-associated molecular patterns (PAMPs, DAMPs), which enables opsonisation or agglutination of non-self or altered/abnormal self cells and contributes to their clearance. The term "cancer" includes a variety of diseases, often incurable, difficult to diagnose and fatal. This short review summarises anti- and pro-tumorigenic associations of SP-A and SP-D as well as perspectives of their usefulness in cancer diagnosis and therapy. Surfactant proteins A and D (SP-A and SP-D) belong to the collectin subfamily of C-type oligomeric lectins. They are pattern-recognition molecules (PRMs), able to recognise pathogen- or danger-associated molecular patterns (PAMPs, DAMPs) in the presence of Ca2+ cations. That property enables opsonisation or agglutination of non-self or altered/abnormal self cells and contributes to their clearance. Like other collectins, SP-A and SP-D are characterised by the presence of four distinct domains: a cysteine-rich domain (at the N-terminus), a collagen-like region, an α-helical neck domain and a globular carbohydrate-recognition domain (CRD) (at the C-terminus). Pulmonary surfactant is a lipoprotein complex, preventing alveolar collapse by reducing surface tension at the air–liquid interface. SP-A and SP-D, produced by type II alveolar epithelial cells and Clara cells, are not only pattern-recognition molecules but also contribute to the surfactant structure and homeostasis. Moreover, they are expressed in a variety of extrapulmonary sites where they are involved in local immunity. The term "cancer" includes a variety of diseases: tumours start from uncontrolled growth of abnormal cells in any tissue which may further spread to other sites of the body. Many cancers are incurable, difficult to diagnose and often fatal. This short review summarises anti- and pro-tumorigenic associations of SP-A and SP-D as well as perspectives of their usefulness in cancer diagnosis and therapy. [ABSTRACT FROM AUTHOR]

Patients with type 2 diabetes have increased risks for dyslipidaemia and subsequently for developing vascular complications. A recent meta-analysis found that cetoleic acid (C22:1n-11) rich fish oils resulted in lower cholesterol concentration in rodents. The aim was to investigate the effect of consuming fish oils with or without cetoleic acid on serum cholesterol concentration in diabetic rats and to elucidate any effects on cholesterol metabolism. Eighteen male Zucker Diabetic Sprague Dawley rats were fed diets containing herring oil (HERO) or anchovy oil (ANCO) or a control diet with soyabean oil for 5 weeks. The HERO diet contained 0·70 % cetoleic acid, with no cetoleic acid in the ANCO diet. The HERO and ANCO diets contained 0·35 and 0·37 wt% EPA + DHA, respectively. Data were analysed using one-way ANOVA. The serum total cholesterol concentration was 14 % lower in the HERO group compared with ANCO and Control groups (P = 0·023). The HERO group had a higher faecal excretion of bile acids (P = 0·0036), but the cholesterol production in the liver, the hepatic secretion of VLDL and the liver's capacity to take up cholesterol were similar to controls. The ANCO diet did not affect the serum cholesterol concentration, but the hepatic cholesterol biosynthesis, the clearance of lipoprotein cholesterol and the excretion of bile acids in faeces were higher than in the Control group. To conclude, consumption of herring oil, but not of anchovy oil, led to a lower cholesterol concentration in a type 2 diabetes rat model. [ABSTRACT FROM AUTHOR]

Background: Lipid droplet (LD) is a metabolically active organelle, which changes dynamically with the metabolic state and energy requirements of cells. Proteins that either insert into the LD phospholipid monolayer or are present in the cytoplasm, playing a crucial role in lipid homeostasis and signaling regulation, are known as LD-associated proteins. Methods: The keywords "lipid droplets" and "metabolic diseases" were used to obtain literature on LD metabolism and pathological mechanism. After searching databases including Scopus, OVID, Web of Science, and PubMed from 2013 to 2024 using terms like "lipid droplets", "lipid droplet-associated proteins", "fatty liver disease", "diabetes", "diabetic kidney disease", "obesity", "atherosclerosis", "hyperlipidemia", "natural drug monomers" and "natural compounds", the most common natural compounds were identified in about 954 articles. Eventually, a total of 91 studies of 10 natural compounds reporting in vitro or in vivo studies were refined and summarized. Results: The most frequently used natural compounds include Berberine, Mangostin, Capsaicin, Caffeine, Genistein, Epigallocatechin-3-gallate, Chlorogenic acid, Betaine, Ginsenoside, Resveratrol. These natural compounds interact with LD-associated proteins and help ameliorate abnormal LDs in various metabolic diseases. Conclusion: Natural compounds involved in the regulation of LDs and LD-associated proteins hold promise for treating metabolic diseases. Further research into these interactions may lead to new therapeutic applications. [ABSTRACT FROM AUTHOR]

Background: Elevated lipoprotein (Lp(a)) levels are associated with increased risk of atherosclerotic processes and cardiovascular events in adults. The amount of Lp(a) is mainly genetically determined. Therefore, it is important to identify individuals with elevated Lp(a) as early as possible, particularly if other cardiovascular risk factors are present. The purpose of the study was to investigate whether, in a population of children and adolescents already followed for the presence of one or more cardiovascular risk factors (elevated blood pressure (BP), and/or excess body weight, and/or dyslipidemia), the measurement of Lp(a) can be useful for better stratifying their risk profile. Methods: In a sample of 195 children and adolescents, height, body weight, waist circumference and systolic (SBP) and diastolic (DBP) BP were measured. Body Mass Index (BMI) and SBP and DBP z-scores were calculated. Plasma Lp(a), total cholesterol, high-density lipoprotein (HDL), triglycerides, glucose, insulin, uric acid and creatinine were assessed. Low-density lipoprotein (LDL) cholesterol was calculated with the Friedewald formula. High Lp(a) was defined as ≥ 75 nmol/L and high LDL cholesterol as ≥ 3.37 mmol/L. Results: Our sample of children and adolescents (54.4% males, mean age 11.5 years) had median LDL cholesterol and Lp(a) values equal to 2.54 (interquartile range, IQR: 2.07–3.06) mmol/L and 22 (IQR: 7.8–68.6) nmol/L respectively. 13.8% of children had LDL cholesterol ≥ 3.37 mmol/L and 22.6 Lp(a) values ≥ 75 nmol/L. Lp(a) values were higher in children of normal weight than in those with excess weight (p = 0.007), but the difference disappeared if normal weight children referred for dyslipidemia only were excluded from the analysis (p = 0.210). 69.4% of children had normal Lp(a) and LDL cholesterol values and only 6.2% showed both elevated Lp(a) and LDL cholesterol levels. However, 16.6% of the sample, despite having normal LDL cholesterol, had elevated Lp(a) values. Multivariable analyses showed a significant association of LDL cholesterol both with Lp(a) values, and with the presence of elevated Lp(a) levels. For each mmol/L increase in LDL cholesterol the risk of having an elevated Lp(a) value increased by 73%. There was an inverse correlation between BMI z-score and Lp(a). Neither BP z-scores, nor other biochemical parameters were associated with Lp(a). Conclusions: In our population more than one out of five children had elevated Lp(a) values, and in about 17% of children elevated Lp(a) values were present in the absence of increased LDL cholesterol. Our results suggest that Lp(a) measurement can be useful to better define the cardiovascular risk profile in children and adolescents already followed for the presence of other cardiovascular risk factors such as elevated BP, excess body weight and high LDL cholesterol. [ABSTRACT FROM AUTHOR]

Atherosclerotic cardiovascular disease (ASCVD) remains a leading cause of morbidity and mortality despite effective low-density lipoprotein cholesterol-targeted therapies. This review explores the crucial role of inflammation in the residual risk of ASCVD, emphasizing its impact on atherosclerosis progression and plaque stability. Evidence suggests that high-sensitivity C-reactive protein (hsCRP), and potentially other inflammatory biomarkers, can be used to identify the inflammatory residual ASCVD risk phenotype and may serve as future targets for the development of more efficacious therapeutic approaches. We review the biological basis for the association of inflammation with ASCVD, propose new therapeutic strategies for the use of inflammation-targeted treatments, and discuss current challenges in the implementation of this new treatment paradigm for ASCVD. [ABSTRACT FROM AUTHOR]

Cell-death-inducing DNA fragmentation factor-alpha (DFFA)-like effector b (CIDEB) was first identified as an apoptosis-inducing protein. Further research revealed a pivotal role in lipid metabolism, regulating very-low-density lipoprotein (VLDL), lipid droplets (LD), sterol response element-binding protein (SREBP), and chylomicrons. Recent studies have uncovered that rare germline variants in CIDEB protect against liver diseases, including MAFLD, cirrhosis, and viral hepatitis. Furthermore, CIDEB influences steps of the hepatitis C virus (HCV) replication cycle. This review summarizes the current knowledge about CIDEB's roles in apoptosis, lipid metabolism, and viral hepatitis, and highlights its critical role in liver diseases. [ABSTRACT FROM AUTHOR]

Over 50% of patients who take statins are still at risk of developing atherosclerotic cardiovascular disease (ASCVD) and do not achieve their goal LDL-C levels. This residual risk is largely dependent on triglyceride-rich lipoproteins (TRL) and their remnants. In essence, remnant cholesterol-rich chylomicron (CM) and very-low-density lipoprotein (VLDL) particles play a role in atherogenesis. These remnants increase when lipoprotein lipase (LPL) activity is inhibited. ApoCIII has been thoroughly studied as a chief inhibitor and therapeutic options to curb its effect are available. On top of apoCIII regulation of LPL activity, there is a more precise control of LPL in various tissues, which makes it easier to physiologically divide the TRL burden according to the body's requirements. In general, oxidative tissues such as skeletal and cardiac muscle preferentially take up lipids during fasting. Conversely, LPL activity in adipocytes increases significantly after feeding, while its activity in oxidative tissues decreases concurrently. This perspective addresses the recent improvements in our understanding of circadian LPL regulations and their therapeutic implications. Three major tissue-specific lipolysis regulators have been identified: ANGPTL3, ANGPTL4, and ANGPTL8. Briefly, during the postprandial phase, liver ANGPTL8 acts on ANGPTL3 (which is released continuously from the liver) to inhibit LPL in the heart and muscle through an endocrine mechanism. On the other hand, when fasting, ANGPTL4, which is released by adipocytes, inhibits lipoprotein lipase in adipose tissue in a paracrine manner. ANGPTL3 inhibitors may play a therapeutic role in the treatment of hypertriglyceridemia. Several approaches are under development. We look forward to future studies to clarify (a) the nature of hormonal and nutritional factors that determine ANGPTL3, 4, and 8 activities, along with what long-term impacts may be expected if their regulation is impaired pharmacologically; (b) the understanding of the quantitative hierarchy and interaction of the regulatory actions of apoCIII, apoAV, and ANGPTL on LPL activity; (c) strategies for the safe and proper treatment of postprandial lipemia; and (d) the effect of fructose restriction on ANGPTL3, ANGPTL4, and ANGPTL8. [ABSTRACT FROM AUTHOR]

Purpose: Metabolic vulnerabilities can exacerbate inflammatory injury and inhibit repair in multiple sclerosis (MS). The purpose was to evaluate whether blood biomarkers of inflammatory and metabolic vulnerability are associated with MS disability and neurodegeneration. Methods: Proton nuclear magnetic resonance spectra were obtained from serum samples from 153 healthy controls, 187 relapsing–remitting, and 91 progressive MS patients. The spectra were analyzed to obtain concentrations of lipoprotein sub-classes, glycated acute-phase proteins, and small-molecule metabolites, including leucine, valine, isoleucine, alanine, and citrate. Composite indices for inflammatory vulnerability, metabolic malnutrition, and metabolic vulnerability were computed. MS disability was measured on the Expanded Disability Status Scale. MRI measures of lesions and whole-brain and tissue-specific volumes were acquired. Results: Valine, leucine, isoleucine, alanine, the Inflammatory Vulnerability Index, the Metabolic Malnutrition Index, and the Metabolic Vulnerability Index differed between healthy control and MS groups in regression analyses adjusted for age, sex, and body mass index. The Expanded Disability Status Scale was associated with small HDL particle levels, inflammatory vulnerability, and metabolic vulnerability. Timed ambulation was associated with inflammatory vulnerability and metabolic vulnerability. Greater metabolic vulnerability and inflammatory vulnerability were associated with lower gray matter, deep gray matter volumes, and greater lateral ventricle volume. Conclusions: Serum-biomarker-derived indices of inflammatory and metabolic vulnerability are associated with disability and neurodegeneration in MS. [ABSTRACT FROM AUTHOR]

Hypertension (HT) is a common chronic disease that often causes target-organ damage and severe complications, contributing to cardiovascular morbidity and mortality worldwide. Accumulating evidence suggests that inflammation plays a prominent role in the initiation and progression of HT. Multiple inflammatory biomarkers have been proposed to predict HT. Several new hematological parameters can reflect the inflammatory response and platelet activation. The major advantage of hematological parameters over conventional inflammatory markers is that they are relatively inexpensive and easily obtained from routine blood tests. Numerous studies have investigated several hematological parameters for their utility as predictive biomarkers for the diagnosis and prognosis of HT. Among them, the neutrophil to lymphocyte ratio (NLR), monocyte to high density lipoprotein cholesterol ratio (MHR), red cell distribution width (RDW), platelet to lymphocyte ratio (PLR), mean platelet volume (MPV), platelet distribution width (PDW), and systemic immune-inflammation index (SII) have recently received attention. We searched PubMed and Embase databases (up to September 18, 2022) to assess the relationships between hematological parameters and HT. This review discusses the diagnostic and prognostic value of these hematological parameters in HT, providing an important basis for early screening, risk stratification, and optimal management of hypertensive patients. [ABSTRACT FROM AUTHOR]

Background: The accurate measurement of blood lipids and lipoproteins is crucial for the clinical management of atherosclerotic disease risk. Despite progress in standardization, there are still significant variations in preanalytical requirements, methods, nomenclature, and reporting work flows. Content: The guidance document aims to improve standardization of clinical lipid testing work flows. It provides recommendations for the components of the lipid panel, fasting requirements, reporting of results, and specific recommendations for non-high-density lipoprotein cholesterol (non-HDL-C), low-density lipoprotein cholesterol (LDL-C), lipoprotein(a) [Lp(a)], apolipoprotein B (apo B), point-of-care lipid testing, and LDL subfraction testing. Summary: Lipid panels should always report non-HDL-C and LDL-C calculations if possible. Fasting is not routinely required except in specific cases. Modern equations should be utilized for LDL-C calculation. These equations allow for LDL-C reporting at elevated concentrations of triglycerides and obviate the need for direct measured LDL-C in most cases. [ABSTRACT FROM AUTHOR]

High‐density lipoproteins (HDLs) play a vital role in lipid metabolism and cardiovascular health, as they are intricately involved in cholesterol transport and inflammation modulation. The proteome of HDL particles is indeed complex and distinct from other components in the bloodstream. Proteomics studies have identified nearly 285 different proteins associated with HDL; however, this review focuses more on the 15 or so traditionally named "apo" lipoproteins. Important lipid metabolizing enzymes closely working with the apolipoproteins are also discussed. Apolipoproteins stand out for their integral role in HDL stability, structure, function, and metabolism. The unique structure and functions of each apolipoprotein influence important processes such as inflammation regulation and lipid metabolism. These interactions also shape the stability and performance of HDL particles. HDLs apolipoproteins have multifaceted roles beyond cardiovascular diseases (CVDs) and are involved in various physiological processes and disease states. Therefore, a detailed exploration of these apolipoproteins can offer valuable insights into potential diagnostic markers and therapeutic targets. This comprehensive review article aims to provide an in‐depth understanding of HDL apolipoproteins, highlighting their distinct structures, functions, and contributions to various physiological processes. Exploiting this knowledge holds great potential for improving HDL function, enhancing cholesterol efflux, and modulating inflammatory processes, ultimately benefiting individuals by limiting the risks associated with CVDs and other inflammation‐based pathologies. Understanding the nature of all 15 apolipoproteins expands our knowledge of HDL metabolism, sheds light on their pathological implications, and paves the way for advancements in the diagnosis, prevention, and treatment of lipid and inflammatory‐related disorders. [ABSTRACT FROM AUTHOR]

Aim: Whether apolipoproteins (apolipoprotein A1, apolipoprotein B, apolipoprotein B/apolipoprotein A1 [ApoB/ApoA1] ratio) or very‐low‐density lipoprotein (VLDL) cholesterol are better risk predictors than established lipid risk markers, and whether there are sex differences, is uncertain, both in general populations and in patients with diabetes. The aim of this study was to assess the association between established risk markers, apolipoproteins and the risk of macro‐ and microvascular disease and death in a large study of women and men with diabetes and to assess the potential sex differences in the associations. Materials and Methods: Established lipid risk markers were studied in 11 140 individuals with type 2 diabetes from the Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified‐Release Controlled Evaluation (ADVANCE) trial, and apolipoproteins (A1, B, ApoB/ApoA1 ratio) and VLDL cholesterol from nuclear magnetic resonance (NMR) lipid analyses in biobanked samples from 3586 individuals included in the ADVANCE case‐cohort study (ADVANCE CC). Primary outcomes were major macro‐ and microvascular events and death. Cox proportional hazards models adjusted for confounders were used to quantify the associations (hazard ratio [HR] and 95% confidence intervals [CIs]) between established lipid risk markers and apolipoproteins with study outcomes. To address potential effect modification by sex, we investigated the association between the lipid risk markers and outcomes in subgroup analyses by sex. Results: There was a lower risk of macrovascular complications for high‐density lipoprotein (HDL) cholesterol (HR [95%CI] 0.88 [0.82–0.95]), a higher risk for total cholesterol (1.10 [1.04–1.17]), low‐density lipoprotein (LDL) cholesterol (1.15 [1.08–1.22]), non‐HDL cholesterol (1.13 [1.07–1.20]) and the total cholesterol/HDL ratio (1.20 [1.14–1.27]) but no significant associations with triglycerides from ADVANCE. There was a higher risk of macrovascular complications for the ApoB/ApoA1 ratio (1.13 [1.03–1.24]) from the ADVANCE CC. Only the ApoB/ApoA1 ratio (1.19 [1.06–1.34]), but none of the established lipid risk markers, was associated with a higher risk of microvascular complications. There were no statistically significant sex differences for any of the established lipid risk markers or apolipoproteins with any outcome. Using C‐statistics and net reclassification improvement (NRI) did not detect significant improvement in predicting all outcomes by adding lipids or apolipoproteins to the models with confounding factors only. Conclusions/Interpretation: All established lipid risk markers, except triglycerides, were predictors of macrovascular complications, but not microvascular complications, in patients with type 2 diabetes. The ApoB/ApoA1 ratio was associated with major macro‐ and microvascular complications, but there was no evidence that apolipoproteins are better than established lipid risk markers in predicting cardiovascular complications in patients with type 2 diabetes. [ABSTRACT FROM AUTHOR]

In recent years, various approaches have been undertaken to eliminate lipoproteins co‐isolated with extracellular vesicles, as they were initially regarded as contaminating entities. However, novel discoveries are reshaping our perspective. In body fluids, these distinct particles not only co‐exist, but also interactions between them are likely to occur. Extracellular vesicles and lipoproteins can associate with each other, share cargo, influence each other's functions, and jointly have a role in the pathomechanisms of diseases. Additionally, their association carries important implications for therapeutic and pharmacological aspects of lipid‐lowering strategies. Extracellular vesicles and lipoprotein particles may have roles in the elimination of each other from the circulation. The objective of this minireview is to delve into these aspects. Here, we show that under certain physiological and pathological conditions, extracellular vesicles and lipoproteins are 'partners' rather than 'strangers' or 'rivals'. [ABSTRACT FROM AUTHOR]

Atherosclerosis is a chronic inflammatory disease of the arterial wall characterized by the accumulation of cholesterol-rich lipoproteins in macrophages. How macrophages commit to proinflammatory polarization under atherosclerosis conditions is not clear. Report here that the level of a circulating protein, leucine-rich alpha-2 glycoprotein 1 (LRG1), is elevated in the atherosclerotic tissue and serum samples from patients with coronary artery disease (CAD). LRG1 stimulated macrophages to proinflammatory M1-like polarization through the activation of extracellular signal-regulated kinase 1/2 (ERK1/2) and c-Jun N-terminal kinase (JNK) pathways. The LRG1 knockout mice showed significantly delayed atherogenesis progression and reduced levels of macrophage-related proinflammatory cytokines in a high-fat diet-induced Apoe-/- mouse atherosclerosis model. An anti-LRG1 neutralizing antibody also effectively blocked LRG1-induced macrophage M1-like polarization in vitro and conferred therapeutic benefits to animals with ApoE deficiency-induced atherosclerosis. LRG1 may therefore serve as an additional biomarker for CAD and targeting LRG1 could offer a potential therapeutic strategy for CAD patients by mitigating the proinflammatory response of macrophages. [ABSTRACT FROM AUTHOR]

Cardiovascular disease is one of the leading causes of death worldwide. Evidence suggests that alterations in the gut microbiome could play a role in cardiovascular diseases, including heart failure. The purpose of this study was to evaluate the effect of synbiotics on serum paraoxonase 1(PON1), soluble CD163/soluble TNF-like weak inducer of apoptosis (sCD163/sTWEAK), and lipid profile, which are involved in heart failure in patients with chronic heart failure. In this triple-blind randomized clinical trial, 90 eligible patients were included in the study. They were randomly assigned to receive one capsule (500 mg) of synbiotics or a placebo daily for ten weeks. Serum PON1, sCD163/sTWEAK, and lipid profiles were measured at the beginning and end of the study. The data were analyzed by SPSS 24, and the p-value < 0.05 was considered statistically significant. Among 90 patients who met the inclusion criteria, 80 completed the study. The primary outcomes showed a small effect on sTWEAK, with an adjusted standard mean difference (SMD) of 0.2. However, no significant changes were observed in sCD163/sTWEAK (SMD: 0.16). Secondary outcomes indicated no changes in PON1, total cholesterol (TC), or LDL-C levels. However, there was an increase in HDL-C levels (adjusted SMD: 0.46, 95% CI: 0.02–0.91) and a decrease in TG and TC/HDL levels (adjusted SMD: − 0.5 and − 0.3, respectively) in the synbiotic group. A favorable effect of synbiotics on sTWEAK, HDL, TG, and TC/HDL of patients with heart failure was observed, but no statistically significant effect was found on sCD163/sTWEAK, PON1, LDL, and TC factors. [ABSTRACT FROM AUTHOR]

Non-alcoholic fatty liver disease (NAFLD) is a progressive liver disease characterized by the build-up of fat in the liver of individuals in the absence of alcohol consumption. This condition has become a burden in modern societies aggravated by the lack of appropriate predictive biomarkers (other than liver biopsy). To better understand this disease and to find appropriate biomarkers, a new technology has emerged in the last two decades with the ability to explore the unmapped role of lipids in this disease: lipidomics. This technology, based on the combination of chromatography and mass spectrometry, has been extensively used to explore the lipid metabolism of NAFLD. In this review, we aim to summarize the knowledge gained through lipidomics assays exploring tissues, plasma, and lipoproteins from individuals with NAFLD. Our goal is to identify common features and active pathways that could facilitate the finding of a reliable biomarker from this field. The most frequent observation was a variable decrease (1–9%) in polyunsaturated fatty acids in phospholipids and non-esterified fatty acids in NAFLD patients, both in plasma and liver. Additionally, a reduction in phosphatidylcholines is a common feature in the liver. Due to the scarcity of studies, further research is needed to properly detect lipoprotein, plasma, and tissue lipid signatures of NAFLD etiologies, and NAFLD subtypes, and to define the relevance of this technology in disease management strategies in the push toward personalized medicine. [ABSTRACT FROM AUTHOR]

Aims: To conduct a pooled analysis of Phase 3 trials investigating the efficacy and safety of inclisiran across glycaemic and body mass index (BMI) strata. Materials and Methods: Participants were randomized 1:1 to receive 300 mg inclisiran sodium or placebo twice yearly, after initial and 3‐month doses up to 18 months, with background oral lipid‐lowering therapy. Analyses were stratified by glycaemic status (normoglycaemia, prediabetes, and diabetes) or BMI (<25, ≥25 to <30, ≥30 to <35, and ≥35 kg/m2). Co‐primary endpoints were percentage and time‐adjusted percentage change in low‐density lipoprotein (LDL) cholesterol from baseline. Safety was also assessed. Results: Baseline characteristics were balanced between treatment arms and across strata. Percent LDL cholesterol change (placebo‐corrected) with inclisiran from baseline to Day 510 ranged from −47.6% to −51.9% and from −48.8% to −54.4% across glycaemic/BMI strata, respectively. Similarly, time‐adjusted percentage changes after Day 90 and up to Day 540 ranged from −46.8% to −52.0% and from −48.6% to −53.3% across glycaemic/BMI strata, respectively. Inclisiran led to significant reductions in proprotein convertase subtilisin/kexin type 9 and other atherogenic lipids and lipoproteins versus placebo across the glycaemic/BMI strata. The proportions of individuals achieving LDL cholesterol thresholds of <1.8 mmol/L and <1.4 mmol/L with inclisiran increased with increasing glycaemic and BMI strata. Across the glycaemic/BMI strata, a higher proportion of individuals had mild/moderate treatment‐emergent adverse events (TEAEs) at the injection site with inclisiran (2.8%–7.7%) versus placebo (0.2%–2.1%). Conclusion: Inclisiran provided substantial and sustained LDL cholesterol lowering across glycaemic/BMI strata, with a modest excess of transient mild‐to‐moderate TEAEs at the injection site. [ABSTRACT FROM AUTHOR]

Despite some reported benefits, there is a low quality of evidence for resistance training (RT) improving metabolic health of individuals with overweight or obesity. We evaluated the impact of RT on body composition, cardiorespiratory fitness (CRF) and physical performance, lipid–lipoprotein profile, inflammation, and glucose–insulin homeostasis in 51 postmenopausal women versus 29 controls matched for age, obesity, and physical activity. Exercised women were further subdivided for comparison of RT effects into those presenting metabolically healthy obesity (MHO) and those with metabolically unhealthy obesity (MUHO) classified according to Karelis and Rabasa-Lhoret or an approach based on adipose tissue secretory dysfunction using the plasma adiponectin(A)/leptin (L) ratio. Participants followed a 4-month weekly RT program targeting major muscle groups (3 × 10 repetitions at 80% one repetition maximum (1-RM)). Percent fat marginally decreased and lean body mass increased (0.01 < p < 0.05) while CRF and muscular strength improved in all women, after RT (effect size (ES): 0.11–1.21 (trivial to large effects), p ˂ 0.01). Fasting plasma triacylglycerol and high-density lipoprotein-cholesterol levels slightly increased and decreased, respectively, in participants with MHO using the A/L ratio approach (ES: −0.47 to 1.07 (small to large effects), p ˂ 0.05). Circulating interleukin-6 soluble receptor decreased in both groups and soluble tumor necrosis factor receptor-1/soluble tumor necrosis factor receptor-2 in women with MUHO only, irrespective of definition (ES: −0.42 to −0.84 (small to large effects), p ˂ 0.05). Glucose–insulin homeostasis was unchanged regardless of group or definition. RT improved physical performance and body composition but had a lesser impact on cardiometabolic risk in women with obesity, irrespective of their metabolic phenotype. [ABSTRACT FROM AUTHOR]

We assessed the effects of consuming a U.S.-style healthy dietary pattern (HDP) with lean, unprocessed beef (BEEF) compared to a U.S.-style HDP without meat (vegetarian, VEG) on short-term changes in cardiometabolic disease (CMD) risk factors in adults classified as overweight or obese. Forty-one adults (22 females, 19 males; age 39.9 ± 8.0 y; BMI 29.6 ± 3.3 kg/m2; mean ± SD) completed two 5-week controlled feeding periods (randomized, crossover, controlled trial). For the BEEF HDP, two 3-oz (168-g) servings/d of lean, unprocessed beef were predominately substituted for some starchy vegetables and refined grains in the VEG HDP. Baseline and post-intervention measurements were fasting CMD risk factors, with serum low-density lipoprotein (LDL), total cholesterol (TC), and total apolipoprotein B as primary outcomes. VEG reduced LDL, insulin, and glucose compared to BEEF. Reductions did not differ between VEG vs. BEEF for TC, high-density lipoprotein (HDL), apolipoprotein A1, small, dense LDL IV, buoyant HDL2b, TC-to-HDL ratio, and systolic blood pressure. Total apolipoprotein B and all other CMD risk factors measured were not influenced by HDP type nor changed over time. Adopting a U.S.-style HDP that is either vegetarian or omnivorous with beef improved multiple cardiometabolic disease risk factors among adults classified as overweight or obese. [ABSTRACT FROM AUTHOR]

Context Cottonseed oil (CSO) is higher in polyunsaturated fatty acids (PUFA) and saturated fatty acids (SFAs) than many liquid plant oils. Objectives To conduct a systematic review of randomized controlled trials (RCTs) examining effects of CSO on markers of lipid metabolism and evaluate lipid and lipoprotein effects of incorporating CSO into a healthy dietary pattern using regression equations. Data Sources A systematic search was conducted for RCTs comparing CSO with a non-CSO comparator in any population. Data Analyses The Katan regression equation was used to predict lipid/lipoprotein changes when incorporating CSO into a US-style healthy eating pattern at 25 to 100% of the total oil allowance (ie, 27 g/2000 kcal) compared with average American intake (NHANES 2017 to 2020 pre-COVID pandemic). Results In total, 3 eligible publications (n = 2 trials), with 58 participants that provided 44% and 30% of total energy as CSO, were included. Fasting low-density lipoprotein cholesterol (LDL-C; ≈ –7.7 mg/dL) and triglycerides (≈ –7.5 mg/dL) were lower after 5 days of a CSO-enriched diet vs olive oil (OO). In a 56-day trial, CSO lowered total cholesterol (TC; ≈ –14.8 mg/dL), LDL-C (≈ –14.0 mg/dL), and non–high-density lipoprotein cholesterol (≈ –14.2 mg/dL) vs OO. Postprandially, angiopoietin-like protein-3, -4, and -8 concentrations decreased with CSO and increased with OO intake. Compared with average American intake, a healthy eating pattern with 27 g of CSO was estimated to lower TC (–8.1 mg/dL) and LDL-C (–7.3 mg/dL) levels, with minimal reduction in high-density lipoprotein cholesterol (–1.1 mg/dL). Compared with the healthy eating pattern, incorporating 27 g of CSO was predicted to increase TC and LDL-C levels by 2.4 mg/dL. Conclusion Limited high-quality research suggests CSO may improve lipid/lipoprotein levels compared with OO. Cholesterol predictive equations suggest CSO can be incorporated into a healthy dietary pattern without significantly affecting lipids/lipoproteins. [ABSTRACT FROM AUTHOR]

Recent advances in human genetics, together with a substantial body of epidemiological, preclinical and clinical trial evidence, strongly support a causal relationship between triglyceride-rich lipoproteins (TRLs) and atherosclerotic cardiovascular disease. Consequently, the secretion and metabolism of TRLs have a significant impact on cardiovascular health. This knowledge underscores the importance of understanding the molecular mechanisms and regulation of very-low-density lipoprotein (VLDL) and chylomicron biogenesis. Fortunately, there has been a resurgence of interest in the intracellular assembly, trafficking, degradation, and secretion of VLDL, leading to many ground-breaking molecular insights. Furthermore, the identification of molecular control mechanisms related to triglyceride metabolism has greatly advanced our understanding of the complex metabolism of TRLs. In this review, we explore recent advances in the assembly, secretion, and metabolism of TRLs. We also discuss available treatment strategies for hypertriglyceridemia. [ABSTRACT FROM AUTHOR]

Enterococcus faecalis is an opportunistic pathogen frequently causing nosocomial infections. The virulence of this organism is underpinned by its capacity to evade phagocytosis, allowing dissemination in the host. Immune evasion requires a surface polysaccharide produced by all enterococci, known as the enterococcal polysaccharide antigen (EPA). EPA consists of a cell wall‐anchored rhamnose backbone substituted by strain‐specific polysaccharides called 'decorations', essential for the biological activity of this polymer. However, the structural determinants required for innate immune evasion remain unknown, partly due to a lack of suitable validated assays. Here, we describe a quantitative, in vitro assay to investigate how EPA decorations alter phagocytosis. Using the E. faecalis model strain OG1RF, we demonstrate that a mutant with a deletion of the locus encoding EPA decorations can be used as a platform strain to express heterologous decorations, thereby providing an experimental system to investigate the inhibition of phagocytosis by strain‐specific decorations. We show that the aggregation of cells lacking decorations is increasing phagocytosis and that this process does not involve the recognition of lipoproteins by macrophages. Collectively, our work provides novel insights into innate immune evasion by enterococci and paves the way for further studies to explore the structure/function relationship of EPA decorations. [ABSTRACT FROM AUTHOR]

The present study outlines the many risk variables of myocardial infarction (MI) in the patient population. Blood lipid profiles were normolipidemic in the study’s subjects. Myocardial infarction patients and controls were compared concerning their lipid, lipoprotein, and apolipoprotein profiles. Materials & methods: In this study, 84 participants had their blood cholesterol, Apolipoprotein-A, LDL, VLDL, HDL, triacylglycerols, and malondialdehyde studied. Out of the total number of participants, 42 were individuals who had suffered a myocardial infarction (MI). In contrast, the other 42 were controls matched for age and sex. Results: Acute myocardial infarction (MI) patients had significantly elevated levels of total cholesterol and triacylglycerols (TAGs) (p <0.05) despite the presence of low-density lipoprotein (LDL) in their blood. A significant difference was seen between the levels of apolipoprotein-A and low-density lipoprotein in the MI group and those in the control group. Researchers found that those who had a rapid heart attack exhibited significantly higher levels of malondialdehyde (p<0.05). Conclusion: For individuals diagnosed with risk factors, lipid profile monitoring, dietary antioxidant consumption, and measurement of inflammatory markers can all help lower the risk of myocardial infarction (MI). Furthermore, early detection can prevent MI. [ABSTRACT FROM AUTHOR]

Background: Metabolic syndrome (MetS) is a cluster of medical conditions and risk factors correlating with insulin resistance that increase the risk of developing cardiometabolic health problems. The specific criteria for diagnosing MetS vary among different medical organizations but are typically based on the evaluation of abdominal obesity, high blood pressure, hyperglycemia, and dyslipidemia. A unique, quantitative and independent estimation of the risk of MetS based only on quantitative biomarkers is highly desirable for the comparison between patients and to study the individual progression of the disease in a quantitative manner. Methods: We used NMR-based metabolomics on a large cohort of donors (n = 21,323; 37.5% female) to investigate the diagnostic value of serum or serum combined with urine to estimate the MetS risk. Specifically, we have determined 41 circulating metabolites and 112 lipoprotein classes and subclasses in serum samples and this information has been integrated with metabolic profiles extracted from urine samples. Results: We have developed MetSCORE, a metabolic model of MetS that combines serum lipoprotein and metabolite information. MetSCORE discriminate patients with MetS (independently identified using the WHO criterium) from general population, with an AUROC of 0.94 (95% CI 0.920–0.952, p < 0.001). MetSCORE is also able to discriminate the intermediate phenotypes, identifying the early risk of MetS in a quantitative way and ranking individuals according to their risk of undergoing MetS (for general population) or according to the severity of the syndrome (for MetS patients). Conclusions: We believe that MetSCORE may be an insightful tool for early intervention and lifestyle modifications, potentially preventing the aggravation of metabolic syndrome. [ABSTRACT FROM AUTHOR]

Leptospirosis, a neglected zoonotic disease, is caused by pathogenic spirochetes belonging to the genus Leptospira and has one of the highest morbidity and mortality rates worldwide. Vaccination stands out as one of the most effective preventive measures for susceptible populations. Within the outer membrane of Leptospira spp., we find the LIC12287, LIC11711, and LIC13259 lipoproteins. These are of interest due to their surface location and potential immunogenicity. Thorough examination revealed the conservation of these proteins among pathogenic Leptospira spp.; we mapped the distribution of T- and B-cell epitopes along their sequences and assessed the 3D structures of each protein. This information aided in selecting immunodominant regions for the development of a chimeric protein. Through gene synthesis, we successfully constructed a chimeric protein, which was subsequently expressed, purified, and characterized. Hamsters were immunized with the chimeric lipoprotein, formulated with adjuvants aluminum hydroxide, EMULSIGEN®-D, Sigma Adjuvant System®, and Montanide™ ISA206VG. Another group was vaccinated with an inactivated Escherichia coli bacterin expressing the chimeric protein. Following vaccination, hamsters were challenged with a virulent L. interrogans strain. Our evaluation of the humoral immune response revealed the production of IgG antibodies, detectable 28 days after the second dose, in contrast to pre-immune samples and control groups. This demonstrates the potential of the chimeric protein to elicit a robust humoral immune response; however, no protection against challenge was achieved. While this study provides valuable insights into the subject, further research is warranted to identify protective antigens that could be utilized in the development of a leptospirosis vaccine. Key points: • Several T- and B-cell epitopes were identified in all the three proteins. • Four different adjuvants were used in vaccine formulations. • Immunization stimulated significant levels of IgG2/3 in vaccinated animals. [ABSTRACT FROM AUTHOR]

Background: Liver lipid dysregulation is one of the major factors in the decline of production performance in late-stage laying hens. Silymarin (SIL), a natural flavonolignan extracted from milk thistle, is known for its hepatoprotective and lipid-lowering properties in humans. This study evaluates whether SIL can provide similar benefits to late-stage laying hens. A total of 480 68-week-old Lohmann Pink laying hens were randomly assigned into 5 groups, each group consisting of 6 replicates with 16 hens each. The birds received a basal diet either without silymarin (control) or supplemented with silymarin at concentrations of 250, 500, 750, or 1,000 mg/kg (SIL250, SIL500, SIL750, SIL1000) over a 12-week period. Results: The CON group exhibited a significant decline in laying rates from weeks 9 to 12 compared to the initial 4 weeks (P = 0.042), while SIL supplementation maintained consistent laying rates throughout the study (P > 0.05). Notably, the SIL500 and SIL750 groups showed higher average egg weight than the CON group during weeks 5 to 8 (P = 0.049). The SIL750 group had a significantly higher average daily feed intake across the study period (P < 0.05), and the SIL500 group saw a marked decrease in the feed-to-egg ratio from weeks 5 to 8 (P = 0.003). Furthermore, the SIL500 group demonstrated significant reductions in serum ALT and AST levels (P < 0.05) and a significant decrease in serum triglycerides and total cholesterol at week 12 with increasing doses of SIL (P < 0.05). SIL also positively influenced liver enzyme expression (FASN, ACC, Apo-VLDL II, FXR, and CYP7A1; P < 0.05) and altered the cecal microbiota composition, enhancing species linked to secondary bile acid synthesis. Targeted metabolomics identified 9 metabolites predominantly involved in thiamin metabolism that were significantly different in the SIL groups (P < 0.05). Conclusions: Our study demonstrated that dietary SIL supplementation could ameliorate egg production rate in late stage laying hens, mechanistically, this effect was via improving hepatic lipid metabolism and cecal microbiota function to achieve. Revealed the potentially of SIL as a feed supplementation to regulate hepatic lipid metabolism dysregulation. Overall, dietary 500 mg/kg SIL had the best effects. [ABSTRACT FROM AUTHOR]

Background: So far, high-density lipoprotein cholesterol (HDL-C) levels and mortality were shown to have a U-shaped relationship. Additionally, high HDL-C levels increase the risk of developing a variety of diseases. However, a paucity of data exists regarding the characteristics of people with high HDL-C levels. The aim of this study was to assess the demographics and characteristics of patients with high HDL-C levels and compare their features with normal and low HDL-C groups. Methods: As a cross-sectional, matched case–control study, a total of 510 patients with type 2 diabetes (T2D) were enrolled in the study and categorized into three matched groups according to their HDL-C concentrations. The studied groups were matched by their age and gender. Restricted cubic spline (RCS) curves were designed to evaluate the relationship between height, blood pressure, triglyceride, and vitamin D concentrations with the probability of having high HDL-C levels. Furthermore, violin plots were conducted to illustrate the distribution of continuous variables within each group. Results: This study showed that having high HDL-C (more than 70 mg/dL) compared to having low HDL-C (less than 40 mg/dL in men and 50 mg/dL in women) was significantly associated with height (OR 0.918, 95% CI 0.866–0.974), systolic blood pressure (SBP) (0.941, 0.910–0.972), vitamin D (0.970, 0.941–0.999), and triglyceride (0.992, 0.987–0.998) serum concentrations. Further analysis investigated that having high HDL-C levels compared to desired HDL-C levels (40 ≤ HDL-C levels < 70 in men and 50 ≤ HDL-C levels < 70 in women) was inversely associated with having SPB values greater than 130 mmHg. Besides, sufficient vitamin D levels (above 20 ng/ml) could 0.349 times decrease the odds of having high HDL-C versus normal HDL-C levels. Conclusion: Sufficient vitamin D levels, SPB values higher than 130 mmHg, as well as increased triglyceride levels, were inversely associated with having high HDL levels. However, higher height values were associated with a decreased likelihood of having high HDL. [ABSTRACT FROM AUTHOR]

On average, LDL particles are the most populous lipoprotein in serum under fasting conditions. For many reasons, it has been the primary target of lipid-lowering guidelines around the world. In the past 30 years, we have witnessed remarkable changes in each iteration of dyslipidaemia guidelines, with LDL-cholesterol (LDL-C) targets becoming lower and lower among patients at high and very high risk for atherosclerotic cardiovascular disease (ASCVD). The world over, goal attainment rates are low, and hence, ASCVD prevalence remains unacceptably high. Inadequate LDL-C lowering is a major issue in contemporary cardiovascular (CV) medicine. Another issue that vexes even the most astute clinician is that of 'residual risk', meaning the excess risk that remains even after LDL-C is appropriately reduced. In recent years, an important new component of residual risk has emerged: triglyceride-enriched lipoproteins or remnant lipoproteins. These precursors to LDL particles can assume outsized importance among patients with derangements in triglyceride metabolism (e.g. genetic variants, insulin resistance, and diabetes mellitus) and may be more atherogenic than LDL species. Consequently, to reduce total risk for acute CV events, the time has come to include the entire spectrum of apoB-containing lipoproteins in approaches to both risk evaluation and treatment. [ABSTRACT FROM AUTHOR]

Lipids are primarily transported in the bloodstream by lipoproteins, which are macromolecules of lipids and conjugated proteins also known as apolipoproteins. The processes of lipoprotein assembly, secretion, transportation, modification, and clearance are crucial components of maintaining a healthy lipid metabolism. Disruption in any of these steps results in pathophysiological abnormalities such as dyslipidemia, obesity, insulin resistance, inflammation, atherosclerosis, peripheral artery disease, and cardiovascular diseases. By studying these genetic mutations, researchers can gain valuable insights into the underlying mechanisms that govern the relationship between protein structure and its physiological role. These lipoproteins, including HDL, LDL, lipoprotein(a), and VLDL, mainly serve the purpose of transporting lipids between tissues and organs. However, studies have provided evidence that apo(a) also possesses protective properties against pathogens. In the future, the field of study will be significantly influenced by the integration of recombinant DNA technology and human site-specific mutagenesis for treating hereditary disorders. Several medications are available for the treatment of dyslipoproteinemia. These include statins, fibrates, ezetimibe, niacin, PCSK9 inhibitors, evinacumab, DPP 4 inhibitors, glucagon-like peptide-1 receptor agonists GLP1RAs, GLP-1, and GIP dual receptor agonists, in addition to SGLT2 inhibitors. This current review article exhibits, for the first time, a comprehensive reflection of the available body of publications concerning the impact of lipoproteins on metabolic well-being across various pathological states. [ABSTRACT FROM AUTHOR]

It is internationally recognized to use clinical decision limits (CDL) when interpreting the lipid levels in both adults and children, even though the evidence for children is scarce. The purpose of this study is to describe how lipid levels progress in healthy Danish children ages 5 to 17 years. This study is based on the Childhood Health, Activity, and Motor Performance School Study Denmark (CHAMPS-study DK) consisting of 1456 observations of schoolchildren aged 5 to 17 years. Participants have been tested for blood levels of total cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglycerides, and remnant cholesterol levels are calculated. Finally, sex-specific percentile reference curves are presented. Percentile reference curves stratified by sex were generated for all cholesterols and showed that the total cholesterol level peaks at 4.32 mmol/l in 10-year-old boys and 4.46 mmol/l in nine-year-old girls. HDL levels in boys peak at 1.72 mmol/l in nine-year-old boys. HDL levels in girls and LDL levels in both sexes are nearly constant. Triglycerides kept rising to the age of 17 years in both sexes and remnant cholesterol decreased from age 5 to 17 years in both sexes. BMI z-score adjustment revealed no significant association with total cholesterol in both sexes but a significant association between HDL, LDL, triglycerides, and remnant cholesterol. This study is the first to generate percentile reference curves for blood levels of total cholesterol, LDL, HDL, triglycerides, and remnant cholesterol in a cohort of healthy Danish children aged 5 to 17 years. [ABSTRACT FROM AUTHOR]

Purpose: To establish prognostic biomarkers of non-prolefarative diabetic retinopathy (NPDR) progression in T2DM on the basis of examination of clinical, ophthalmological and laboratory (carbohydrate and lipid metabolism and coagulation and hemostasis) characteristics. Methods: This study included 358 T2DM2 patients with diabetic retinopathy (DR); for each patient, the eye with more severe DR was included in the study. Cases were dichotomized into three groups based on DR severity: group 1 (NPDR; 189 eyes), group 2 (preproliferative DR or PPDR; 96 eyes), and group 3 (proliferative DR or PDR; 73 eyes). Central retinal thickness (CRT; µm) and central retinal volume (CRV) were assessed by optical coherence tomography (OCT; mm3). Serum samples were taken to assess fasting serum glucose, glycosylated hemoglobin (HbA1c), total cholesterol, highdensity lipoprotein (HDL), low-density lipoprotein (LDL), very low-density lipoprotein (VLDL), triglycerides, and fibrinogen. Coagulation and hemostasis parameters were assessed. Statistical analyses were performed with EZR version 1.54. Results: Associations of the variables with the risk of NPDR progression were confirmed by a univariate logistic regression analysis. The area under curve (AUC) was largest for HbA1c (AUC = 0.84), followed by CRT and CRV (AUC = 0.79). In addition, the AUC ranged from 0.56 to 0.67 for the rest of variables. Age, gender, diabetes duration, and blood HDL level were not associated with NPDR progression. Our multivatiate logistic regression analysis found six biomarkers (age, HbA1c, LDL, VLDL, prothrombin index and CRT) directly associated with the risk of NPDR progression (AUC = 0.91; p < 0.001). The established association was mostly due to the three independent variables, HbA1c, VLDL and CRT (AUC = 0.90; p < 0.001). Conclusion: Independent effects on the risk of NPDR progression were confirmed for HbA1c, VLDL and CRT. The built model was found to be of very high predictive quality, which allowed recommending it for confirming high risk for NPDR progression in equivocal clinical cases or as a criterion for conclusive prognosis in the relevant expert systems. [ABSTRACT FROM AUTHOR]

The liver plays a key role in the metabolism of lipoproteins, controlling both production and catabolism. To accelerate the development of new lipid‐lowering therapies in humans, it is essential to have a relevant in vitro study model available. The current hepatocyte‐like cells (HLCs) models derived from hiPSC can be used to model many genetically driven diseases but require further improvement to better recapitulate the complexity of liver functions. Here, we aimed to improve the maturation of HLCs using a three‐dimensional (3D) approach using Biomimesys®, a hyaluronic acid‐based hydroscaffold in which hiPSCs may directly form aggregates and differentiate toward a functional liver organoid model. After a 28‐day differentiation 3D protocol, we showed that many hepatic genes were upregulated in the 3D model (liver organoids) in comparison with the 2D model (HLCs). Liver organoids, grown on Biomimesys®, exhibited an autonomous cell organization, were composed of different cell types and displayed enhanced cytochromes P450 activities compared to HLCs. Regarding the functional capacities of these organoids, we showed that they were able to accumulate lipids (hepatic steatosis), internalize low‐density lipoprotein and secrete apolipoprotein B. Interestingly, we showed for the first time that this model was also able to produce apolipoprotein (a), the apolipoprotein (a) specific of Lp(a). This innovative hiPSC‐derived liver organoid model may serve as a relevant model for studying human lipopoprotein metabolism, including Lp(a). [ABSTRACT FROM AUTHOR]

The elderly population is at a higher risk of cardiovascular complications, and dyslipidemia plays a significant role as a contributing factor. Chronic kidney disease (CKD) patients are prone to lipid abnormalities, further increasing the risk of cardiovascular complications. We aimed to investigate the lipid profile characteristics of the middle‐aged and elderly population, particularly CKD patients. We conducted a cross‐sectional study using baseline data from the Systolic Blood Pressure Intervention Trial (SPRINT). It was examined how lipid profiles are affected by age within the general population, and how BMI and lipid characteristics are affected by CKD subtype. Among 8746 participants, we observed a decreasing trend in LnTAG (natural logarithm of Triacylglycerol) and total Cholesterol (CHR) levels with increasing age, while high‐density lipoprotein cholesterol (HDL‐C) levels increased with age. In the CKD and non‐CKD subgroups created through propensity score matching based on age, sex, and race, CKD individuals exhibited significantly higher average LnTAG levels across all age groups compared to the non‐CKD group. Multivariable linear regression analysis, controlling for confounding variables, revealed a negative correlation between LnTAG and estimated glomerular filtration rate (eGFR) (r = −0.002, p < 0.001). HDL‐C showed a positive correlation with eGFR (r = 0.001, p < 0.001). [Correction added on 1 July 2024, after first online publication: The value of r in the preceding sentence has been updated to r = 0.001.] That is, in the middle‐aged and elderly population, age demonstrated a negative correlation with total CHR and TAG levels, while exhibiting a positive correlation with HDL‐C levels. CKD patients exhibited relatively higher TAG levels, which were positively associated with CKD progression. [ABSTRACT FROM AUTHOR]

The monocyte‐to‐high‐density lipoprotein cholesterol ratio (MHR) is a novel marker that can help estimate the degree of atherosclerosis by considering inflammation and lipid abnormalities. This study aimed to assess the association between the MHR and prevalent heart failure (HF) and to explore the value of the MHR in detecting prevalent HF in the general US population. Our study included 25,374 participants from the National Health and Nutrition Examination Survey (1999–2018). Among the participants, 749 (2.95%) reported a history of HF, and the HF group had a significantly higher MHR than the non‐HF group. Adjusted analyses revealed that each standard deviation increase in the MHR was associated with a 27.8% increase in the risk of HF. The association between the MHR and prevalent HF was linear across the entire MHR range. Adding the MHR to conventional cardiovascular risk factors significantly improved the area under the curve (0.875; p < 0.001), continuous net reclassification index (0.187; p < 0.001), and integrated discrimination index (0.004; p < 0.001). Our study suggests a potential association between the MHR and HF risk, and the findings enhance HF risk stratification and provide novel insights into the interplay between the coronary atherosclerotic burden and HF in clinical settings. [ABSTRACT FROM AUTHOR]

The molecular mechanisms that govern the metabolic commitment to reproduction, which often occurs at the expense of somatic reserves, remain poorly understood. We identified the Caenorhabditis elegans F-box protein FBXL-5 as a negative regulator of maternal provisioning of vitellogenin lipoproteins, which mediate the transfer of intestinal lipids to the germline. Mutations in fbxl-5 partially suppress the vitellogenesis defects observed in the heterochronic mutants lin-4 and lin-29, both of which ectopically express fbxl-5 at the adult developmental stage. FBXL-5 functions in the intestine to negatively regulate expression of the vitellogenin genes; and consistently, intestine-specific over-expression of FBXL-5 is sufficient to inhibit vitellogenesis, restrict lipid accumulation, and shorten lifespan. Our epistasis analyses suggest that fbxl-5 functions in concert with cul-6, a cullin gene, and the Skp1-related gene skr-3 to regulate vitellogenesis. Additionally, fbxl-5 acts genetically upstream of rict-1, which encodes the core mTORC2 protein Rictor, to govern vitellogenesis. Together, our results reveal an unexpected role for a SCF ubiquitin-ligase complex in controlling intestinal lipid homeostasis by engaging mTORC2 signaling. [ABSTRACT FROM AUTHOR]

Background and aims: The impact of lipids on the overall survival (OS) of patients with malignancy has not yet been clarified. This study aimed to evaluate the effect of hyperlipidemia on the OS among Chinese patients based on Body Mass Index (BMI) stratifications and hyperlipidemia types. Method: The patients in this study were derived from the Investigation of the Nutrition Status and Clinical Outcome of Common Cancers (INSCOC) trial. Kaplan–Meier was used to draw the survival curve, and the log-rank test was used to estimate the survival rates between each group. Cox proportional hazards regression models were used to estimate the hazard ratios (HR) and 95% confidence intervals (CI). Results: A total of 9054 patients were included in the final study, with a median age of 59 years, and 55.3% (5004) of them were males. Regarding types of hyperlipidemia, only low high-density lipoprotein was an independent risk factor for the prognosis of all patients (HR = 1.35, 95% CI: 1.25–1.45, P < 0.001), while high total cholesterol (HR = 1.01, 95% CI: 0.90–1.15, P = 0.839) and high low-density lipoprotein (HR = 1.03, 95%CI: 0.91–1.16, P = 0.680) were not. In terms of BMI stratification, the effect of triglycerides on prognosis varied; high triglycerides were an independent risk factor for the prognosis of underweight patients (HR = 1.56, 95% CI:1.05–2.32, P = 0.027) and a protective factor for overweight patients (HR = 0.75, 95% CI: 0.63–0.89, P = 0.001). However, for normal-weight patients, there was no significant statistical difference (HR = 0.88, 95%CI: 0.75–1.03, P = 0.108). Conclusions: The impact of hyperlipidemia on the OS among patients with cancer varied by different BMI and hyperlipidemia types. BMI and hyperlipidemia type ought to be considered in combination to estimate the prognosis of patients with malignancy. [ABSTRACT FROM AUTHOR]

Serum amyloid A (SAA) proteins are highly conserved lipoproteins that are notoriously involved in the acute phase response and systemic amyloidosis, but their biological functions are incompletely understood. Recent work has shown that SAA proteins can enter the brain by crossing the intact blood–brain barrier (BBB), and that they can impair BBB functions. Once in the central nervous system (CNS), SAA proteins can have both protective and harmful effects, which have important implications for CNS disease. In this review of the thematic series on SAA, we discuss the existing literature that relates SAA to neuroinflammation and CNS disease, and the possible roles of the BBB in these relations. [ABSTRACT FROM AUTHOR]

The global prevalence of cardiovascular diseases (CVD) continues to rise steadily, making it a leading cause of mortality worldwide. Atherosclerosis (AS) serves as a primary driver of these conditions, commencing silently at an early age and culminating in adverse cardiovascular events that severely impact patients’ quality of life or lead to fatality. Dyslipidemia, particularly elevated levels of low-density lipoprotein cholesterol (LDL-C), plays a pivotal role in AS pathogenesis as an independent risk factor. Research indicates that abnormal LDL-C accumulation within arterial walls acts as a crucial trigger for atherosclerotic plaque formation. As the disease progresses, plaque accumulation may rupture or dislodge, resulting in thrombus formation and complete blood supply obstruction, ultimately causing myocardial infarction, cerebral infarction, and other common adverse cardiovascular events. Despite adequate pharmacologic therapy targeting LDL-C reduction, patients with cardiometabolic abnormalities remain at high risk for disease recurrence, highlighting the importance of addressing lipid risk factors beyond LDL-C. Recent attention has focused on the causal relationship between triglycerides, triglyceride-rich lipoproteins (TRLs), and their remnants in AS risk. Genetic, epidemiologic, and clinical studies suggest a causal relationship between TRLs and their remnants and the increased risk of AS, and this dyslipidemia may be an independent risk factor for adverse cardiovascular events. Particularly in patients with obesity, metabolic syndrome, diabetes, and chronic kidney disease, disordered TRLs and its remnants levels significantly increase the risk of atherosclerosis and cardiovascular disease development. Accumulation of over-synthesized TRLs in plasma, impaired function of enzymes involved in TRLs lipolysis, and impaired hepatic clearance of cholesterol-rich TRLs remnants can lead to arterial deposition of TRLs and its remnants, promoting foam cell formation and arterial wall inflammation. Therefore, understanding the pathogenesis of TRLs-induced AS and targeting it therapeutically could slow or impede AS progression, thereby reducing cardiovascular disease morbidity and mortality, particularly coronary atherosclerotic heart disease. [ABSTRACT FROM AUTHOR]