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Abstract: Hippo, an evolutionarily conserved kinase cascade reaction in organisms, can respond to a set of signals, such as mechanical signals and cell metabolism, to maintain cell growth, differentiation, tissue/organ development, and homeostasis. In the past ten years, Hippo has controlled the development of tissues and organs by regulating the process of cell proliferation, especially in the field of cardiac regeneration after myocardial infarction. This suggests that Hippo signaling is closely linked to cardiovascular disease. Atherosclerosis is the most common disease of the cardiovascular system. It is characterised by chronic inflammation of the vascular wall, mainly involving dysfunction of endothelial cells, smooth muscle cells, and macrophages. Oxidized Low density lipoprotein (LDL) damages the barrier function of endothelial cells, which enter the middle membrane of the vascular wall, accelerate the formation of foam cells, and promote the occurrence and development of atherosclerosis. Autophagy is associated with the development of atherosclerosis. However, the mechanism of Hippo regulation of atherosclerosis has not meant to be clarified. In view of the pivotal role of this signaling pathway in maintaining cell growth, proliferation, and differentiation, the imbalance of Hippo is related to atherosclerosis and related diseases. In this review, we emphasized Hippo as a hub for regulating atherosclerosis and discussed its potential targets in pathophysiology, human diseases, and related pharmacology.

Inflammation is a double-edged sword. The moderate inflammatory response is a fundamental defense mechanism produced by the body's resistance to dangerous stimuli and a repair process of the body itself. Increasing studies have confirmed that the overactivation of the inflammasome is involved in the occurrence and development of inflammatory diseases. Strictly controlling the overactivation of the inflammasome and preventing excessive inflammatory response have always been the research focus on inflammatory diseases. However, the endogenous regulatory mechanism of inflammasome is not completely clear. The tripartite motif (TRIM) protein is one of the members of E3 ligases in the process of ubiquitination. The universality and importance of the functions of TRIM members are recognized, including the regulation of inflammatory response. This article will focus on research on the relationship between TRIMs and NLRP3 Inflammasome, which may help us make some references for future related research and the discovery of treatment methods.

Proprotein convertase subtilisin/Kexin type 9 (PCSK9) is a secretory serine protease that plays multiple biological functions in the regulation of physiological and pathological processes. PCSK9 inhibitors decrease the circulating LDL-cholesterol level with well-known preventive and therapeutic effects on atherosclerosis (AS). Still, increasing evidence shows that the direct impact of PCSK9 on the vascular wall also plays an important role in atherosclerotic progression. Compared with other vascular cells, a large proportion of PCSK9 is originated from vascular smooth muscle cells (VSMC). Therefore, defining the effect of VSMC-derived PCSK9 on response changes, such as phenotypic switch, apoptosis, autophagy, inflammation, foam cell formation, and calcification of VSMC, helps us better understand the “pleiotropic” effects of VSMC on the atherosclerotic process. In addition, our understanding of the mechanisms of PCSK9 controlling VSMC functions in vivo is far from enough. This review aims to holistically evaluate and analyze the current state of our knowledge regarding PCSK9 actions affecting VSMC functions and its mechanism in atherosclerotic lesion development. A mechanistic understanding of PCSK9 effects on VSMC will further underpin the success of a new therapeutic strategy targeting AS.

Diabetic cardiomyopathy (DCM) is a cardiovascular complication that tends to occur in patients with diabetes, obesity, or insulin resistance, with a higher late mortality rate. Sustained hyperglycemia, increased free fatty acids, or insulin resistance induces metabolic disorders in cardiac tissues and cells, leading to myocardial fibrosis, left ventricular hypertrophy, diastolic and/or systolic dysfunction, and finally develop into congestive heart failure. The close connection between all signaling pathways and the complex pathogenesis of DCM cause difficulties in finding effective targets for the treatment of DCM. It reported that hydrogen sulfide (H2S) could regulate cell energy substrate metabolism, reduce insulin resistance, protect cardiomyocytes, and improve myocardial function by acting on related key proteins such as differentiation cluster 36 (CD36) and glucose transporter 4 (GLUT4). In this article, the relative mechanisms of H2S in alleviating metabolic disorders of DCM were reviewed, and how H2S can better prevent and treat DCM in clinical practice will be discussed.

Abstract: An abdominal aortic aneurysm (AAA) is a progressive dilatation of the vascular wall occurring below the aortic fissure, preferably occurring below the renal artery. The molecular mechanism of AAA has not yet been elucidated. In the past few decades, research on abdominal aortic aneurysm has been mainly focused on the vessel wall, and it is generally accepted that inflammation and middle layer fracture of the vessel wall is the core steps in the development of AAA. However, perivascular adipose tissue plays a non-negligible role in the occurrence and development of AAA. The position of PVAT plays a supporting and protective role on the vascular wall, but the particularity of the location makes it not only have the physiological function of visceral fat; but also can regulate the vascular function by secreting a large number of adipokines and cytokines. An abdominal aortic aneurysm is getting higher and higher, with a vascular rupture, low rescue success rate, and extremely high lethality rate. At present, there is no drug to control the progression or reverse abdominal aortic aneurysm. Therefore, it is critical to deeply explore the mechanism of abdominal aortic aneurysms and find new therapeutic ways to inhibit abdominal aortic aneurysm formation and disease progression. An abdominal aortic aneurysm is mainly characterized by inflammation of the vessel wall and matrix metalloprotein degradation. In this review, we mainly focus on the cytokines released by the perivascular adipose tissue, summarize the mechanisms involved in the regulation of abdominal aortic aneurysms, and provide new research directions for studying abdominal aortic aneurysms.

Endothelial–mesenchymal transition (EndMT) is widely involved in the occurrence and development of cardiovascular diseases. Although there is no direct evidence, it is very promising as an effective target for the treatment of these diseases. Endothelial cells need to respond to the complex cardiovascular environment through EndMT, but sustained stimuli will cause the imbalance of EndMT. Blocking the signal transduction promoting EndMT is an effective method to control the imbalance of EndMT. In particular, we also discussed the potential role of endothelial cell apoptosis and autophagy in regulating the imbalance of EndMT. In addition, promoting mesenchymal-endothelial transformation (MEndT) is also a method to control the imbalance of EndMT. However, targeting EndMT to treat cardiovascular disease still faces many challenges. By reviewing the research progress of EndMT, we have put forward some insights and translated them into challenges and opportunities for new treatment strategies for cardiovascular diseases.

Atherosclerosis is a chronic arterial wall illness that forms atherosclerotic plaques within the arteries. Plaque formation and endothelial dysfunction are atherosclerosis' characteristics. It is believed that the occurrence and development of atherosclerosis mainly include endothelial cell damage, lipoprotein deposition, inflammation and fibrous cap formation, but its molecular mechanism has not been elucidated. Therefore, protecting the vascular endothelium from damage is one of the key factors against atherosclerosis. The factors and processes involved in vascular endothelial injury are complex. Finding out the key factors and mechanisms of atherosclerosis caused by vascular endothelial injury is an important target for reversing and preventing atherosclerosis. Changes in cell adhesion are the early characteristics of EndMT, and cell adhesion is related to vascular endothelial injury and atherosclerosis. Recent researches have exhibited that endothelial-mesenchymal transition (EndMT) can urge atherosclerosis' progress, and it is expected that inhibition of EndMT will be an object for anti-atherosclerosis. We speculate whether inhibition of EndMT can become an effective target for reversing atherosclerosis by improving cell adhesion changes and vascular endothelial injury. Studies have shown that H2S has a strong cardiovascular protective effect. As H2S has anti- inflammatory, anti-oxidant, inhibiting foam cell formation, regulating ion channels and enhancing cell adhesion and endothelial functions, the current research on H2S in cardiovascular aspects is increasing, but anti-atherosclerosis's molecular mechanism and the function of H2S in EndMT have not been explicit. In order to explore the mechanism of H2S against atherosclerosis, to find an effective target to reverse atherosclerosis, we sum up the progress of EndMT promoting atherosclerosis, and Hydrogen sulfide's potential anti- EndMT effect is discussed in this review.

BACKGROUND Malnutrition is highly prevalent in critically ill patients. The modified Nutrition Risk in the Critically ill (mNUTRIC) score has been introduced to evaluate the nutritional risk of patients in an intensive care unit (ICU). The mNUTRIC score is a predictive factor of mortality for patients in a medical or mixed ICU, whereas the relationship between mNUTRIC and prognosis of patients in a cardiothoracic surgery recovery unit (CSRU) is unclear and related researches are limited. METHODS We conducted this retrospective cohort study to explore the value of mNUTRIC score in CSRU patients. We identified totally 4059 patients from the Multiparameter Intelligent Monitoring in Intensive Care III (MIMIC III) database. RESULTS The optimal cut-off value of mNUTRIC score was 4 and a total of 1498 (36.9%) patients were considered to be at high nutritional risk (mNUTRIC ≥ 4). A multivariate logistic regression model indicated that patients at high nutritional risk have higher hospital mortality compared to those at low nutritional risk (odds ratio = 2.49, 95% confidence interval (CI) = 1.32-4.70, p = 0.005]. Furthermore, a Cox regression model was established adjusted for age, white blood cell and body mass index. The Kaplan-Meier curve indicated that patients at high nutritional risk have poorer 365-days [hazard ratio (HR) = 1.76, 95% CI = 1.30-2.37, p

Abdominal aortic aneurysms (AAA) are permanent and irreversible local dilatations of the abdominal aortic wall. Recent data indicate that the transforming growth factor-beta (TGF-β) signaling pathway exerts a protective effect on the development of AAA. Some dysregulated microRNAs (miRNA) also appear involved in the expansion of AAA and miRNA-based therapeutics have been shown to effectively inhibit this process. New evidence has revealed that TGF-β signaling and miRNA interaction may of physiologic and pathophysiologic significance including the progression of AAA. As such, miRNA that regulate TGF-β signaling may hold promise as potential therapeutic targets. This review explores potential crosstalk between TGF-β signaling and miRNA in AAA in order improve our understanding of this pathology and explore development of potential therapeutic targets.

Coronary heart disease (CHD) is closely related to hypercholesterolemia, and lowering serum cholesterol is currently the most important strategy in reducing CHD. In humans, the serum cholesterol level is determined mainly by three metabolic pathways, namely, dietary cholesterol intake, cholesterol synthesis, and cholesterol degradation in vivo. An intervention that targets the key molecules in the three pathways is an important strategy in lowering serum lipids. Statins inhibit 3-hydroxyl-3-methylglutaryl coenzyme A reductase (HMG-CoA reductase) to reduce low-density lipoprotein (LDL) by about 20% to 45%. However, up to 15% of patients cannot tolerate the potential side effects of high statin dosages, and several patients also still do not reach their optimal LDL goals after being treated with statins. Ezetimibe inhibits cholesterol absorption by targeting the Niemann–Pick C1-like 1 protein (NPC1L1), which is related to cholesterol absorption in the intestines. Ezetimibe lowers LDL by about 18% when used alone and by an additional 25% when combined with statin therapy. The proprotein convertase subtilisin/kexin type 9 (PCSK9) increases hepatic LDLR degradation, thereby reducing the liver’s ability to remove LDL, which can lead to hypercholesterolemia. Evolocumab, which is a PCSK9 monoclonal antibody, can reduce LDL from baseline by 53% to 56%. The three drugs exert lipid-lowering effects by regulating the three key pathways in lipid metabolism. Combining any with the two other drugs on the basis of statin treatment has improved the lipid-lowering effect. Whether the combination of the three musketeers will reduce the side effects of monotherapy and achieve the lipid-lowering effect should be studied further in the future.

Atherosclerosis is a chronic inflammatory vascular disease. Atherosclerotic cardiovascular disease is the main cause of death in both developed and developing countries. Many pathophysiological factors, including abnormal cholesterol metabolism, vascular inflammatory response, endothelial dysfunction and vascular smooth muscle cell proliferation and apoptosis, contribute to the development of atherosclerosis and the molecular mechanisms underlying the development of atherosclerosis are not fully understood. Ubiquitination is a multistep post-translational protein modification that participates in many important cellular processes. Emerging evidence suggests that ubiquitination plays important roles in the pathogenesis of atherosclerosis in many ways, including regulation of vascular inflammation, endothelial cell and vascular smooth muscle cell function, lipid metabolism and atherosclerotic plaque stability. This review summarizes important contributions of various E3 ligases to the development of atherosclerosis. Targeting ubiquitin E3 ligases may provide a novel strategy for the prevention of the progression of atherosclerosis.

Absent in melanoma 2 (AIM2) is a member of the PYHIN (pyrin and HIN domain-containing protein) family with important roles in sensing double-stranded DNA (dsDNA) and assembling the AIM2 inflammasome, which has wide-ranging, pro-inflammatory and pro-pyroptotic properties. The AIM2 inflammasome can become activated in atherosclerotic plaque, abdominal aortic aneurysm wall and injured myocardium, and its activation is tightly regulated by a variety of atherogenic factors. Activation of the AIM2 inflammasome has close links to the progression of several cardiovascular diseases. This review will summarize the current knowledge of AIM2 biology, providing the latest insights into the mechanisms and contributions of atherogenic factors to AIM2 inflammasome activation. In addition, we will also explore crosstalk between AIM2 and the pathologies of atherosclerosis, abdominal aortic aneurysm, myocardial infarction and heart failure. A better understanding of the pathological roles of AIM2 in these disorders will be helpful in developing novel therapeutic approaches.

Background It is of important clinical significance for hepatocellular carcinoma (HCC) patients to evaluate prognosis before interventional embolotherapy. Methods A total of 106 patients with HCC after interventional embolotherapy who had complete data with follow-up information until September 2019 were included in this study. These data were analyzed using SPSS Version 22.0 and R (version 3.6.1) statistical software. Results 1) The diameter of the tumor, ascites, FIT, AFP, ALT, AST, GGT, and Child–Pugh score had the ability to predict the prognosis and survival of patients with HCC. Among these molecules, the predictive effectiveness (or the area under the receiver operating characteristic [ROC] curve) of GGT was the highest, although it was slightly lower than the predictive effectiveness of the Child–Pugh score, which is the gold standard for survival analysis. 2) Among survival analyses combining five molecular indicators, the predictive postoperative viability for combination 1 was the strongest with an area under the ROC curve (AUC) of 0.856 (0.779, 0.932), similar to the all-molecular combination (combination 16) with an AUC of 0.872 (0.798, 0.945), but much higher than that of the Child–Pugh score of 0.720 (0.616, 0.823) for HCC patients (all p

Abstract: Ferroptosis, is an iron-dependent cell death, characterized by the accumulation of lipid reactive oxygen species, and various regulatory mechanisms influence the course of ferroptosis. The rapid increase in cardiovascular diseases(CVDs) is an extremely urgent problem. CVDs are characterized by the progressive deterioration of the heart and blood vessels, eventually leading to circulatory system disorder. Accumulating evidence, however, has highlighted crucial roles for ferroptosis in CVDs. Hydrogen sulfide plays a significant part in anti-oxidative stress, which may participate in the general mechanism of ferroptosis and regulate it by some signaling molecules. This review primarily summarized the effects of hydrogen sulfide on ferroptosis and cardiovascular disease, especially its antioxidative stress, and would provide a more effective direction for the clinical study of CVDs.

An electrochemical sulfonylation reaction of styrenes was developed in which sodium arylsulfinates were used as sulfonylating reagents, a catalytic amount of KI was used as a redox mediator, and Bu4NBF4 was used as the electrolyte. In addition to various styrenes, sodium arylsulfinates with either electron-donating or electron-withdrawing groups were tolerated.

Hydrogen sulfide (H2S), a novel gaseous signaling molecule, is a vital physiological signal in mammals. H2S protects the cardiovascular system via modulation of vasodilation, vascular remodeling, and inhibition of vascular calcification, and also has anti-atherosclerosis properties. Autophagy is a lysosomal-mediated intracellular degradation mechanism for excessive or abnormal proteins and lipids. The contribution of autophagy to normal and disease-state cell physiology is extremely complicated. Autophagy acts as a double-edged sword in the cardiovascular system. It can defend against damage to cells caused by environmental changes and it can also induce active cell death under certain conditions. In recent years, accumulating evidence indicates that H2S can up- or downregulate autophagy in many pathological processes, thereby switching from a harmful to a beneficial role. In this review, we summarize progress on understanding the mechanism by which H2S regulates autophagy in cardiovascular disease. We also discuss a H2S switch phenomenon that regulates autophagy and provides protection in cardiovascular diseases.

Atherosclerosis is a chronic inflammatory response that increases the risk of cardiovascular diseases. An in-depth study of the pathogenesis of atherosclerosis is critical for the treatment of atherosclerotic cardiovascular disease. The development of atherosclerosis involves many cells, such as endothelial cells, vascular smooth muscle cells, macrophages, and others. The considerable effects of macrophages in atherosclerosis are inextricably linked to macrophage polarization and the resulting phenotype. Moreover, the significant impact of macrophages on atherosclerosis depend not only on the function of the different macrophage phenotypes but also on the relative ratio of different phenotypes in the plaque. Research on atherosclerosis therapy indicates that the reduced plaque size and enhanced stability are partly due to modulating macrophage polarization. Therefore, regulating macrophage polarization and changing the proportion of macrophage phenotypes in plaques is a new therapeutic approach for atherosclerosis. This review provides a new perspective for atherosclerosis therapy by summarizing the relationship between macrophage polarization and atherosclerosis, as well as treatment targeting macrophage polarization.

Accumulation of reactive oxygen species (ROS) can induce both protein tyrosine nitration and endothelial dysfunction in atherosclerosis. Endothelial dysfunction refers to impaired endothelium-dependent vasorelaxation that can be triggered by an imbalance in nitric oxide (NO) production and consumption. ROS reacts with NO to generate peroxynitrite, decreasing NO bioavailability. Peroxynitrite also promotes protein tyrosine nitration in vivo that can affect protein structure and function and further damage endothelial function. In this review, we discuss the process of protein tyrosine nitration, increased expression of nitrated proteins in cardiovascular disease and their association with endothelial dysfunction, and the interference of tyrosine nitration with antioxidants and the protective role in endothelial dysfunction. These may lead us to the conception that protein tyrosine nitration may be one of the causes of endothelial dysfunction, and help us gain information about the mechanism of endothelial dysfunction underlying atherosclerosis.

Atherosclerosis (AS) is the pathological basis of numerous lethal diseases, such as myocardial infarction, heart failure, and stroke. As we know, almost twenty million people worldwide die of the arterial diseases annually. Sestrin2 is a stress-inducing protein, which serves as a guardian by activating AMPK, inhibiting mTOR, and maintaining redox balance beneath various stress environments. A large number of studies show that Sestrin2 would shield the body from injury by stress. Moreover, it has been demonstrated that Sestrin2 is closely connected with AS. Here, this article reviewed the involvement of Sestrin2 in the pathogenesis of AS from four aspects: cellular mechanism, oxidative stress, inflammation, and lipid metabolism. Current evidence reveals that Sestrin2 is a novel target for the prevention and treatment of AS.

Although the adhesion molecules-mediated leukocyte adherence and infiltration into tissues is an important step of inflammation, the post-translational regulation of these proteins on the endothelial cells is poorly understood. Here, we report that TRIM65, an ubiquitin E3 ligase of tripartite protein family, selectively targets vascular cell adhesion molecule 1 (VCAM-1) and promotes its ubiquitination and degradation, by which it critically controls the duration and magnitude of sepsis-induced pulmonary inflammation. TRIM65 is constitutively expressed in human vascular endothelial cells. During TNFα-induced endothelial activation, the protein levels of TRIM65 and VCAM-1 are inversely correlated. Expression of wild-type TRIM65, but not expression of a TRIM65 mutant that lacks E3 ubiquitin ligase function in endothelial cells, promotes VCAM-1 ubiquitination and degradation, whereas small interference RNA-mediated knockdown of TRIM65 attenuates VCAM-1 protein degradation. Further experiments show that TRIM65 directly interacts with VCAM-1 protein and directs its polyubiquitination, by which TRIM65 controls monocyte adherence and infiltration into tissues during inflammation. Importantly, TRIM65-deficient mice are more sensitive to lipopolysaccharide-induced death, due to sustained and severe pulmonary inflammation. Taken together, our studies suggest that TRIM65-mediated degradation of VCAM-1 represents a potential mechanism that controls the duration and magnitude of inflammation.

Tissue factor pathway inhibitor (TFPI) reduces the development of atherosclerosis by regulating tissue factor (TF) mediated coagulation pathway. In this review, we focus on recent findings on the inhibitory effects of TFPI on endothelial cell activation, vascular smooth muscle cell (VSMC) proliferation and migration, inflammatory cell recruitment and extracellular matrix which are associated with the development of atherosclerosis. Meanwhile, we are also concerned about the impact of TFPI levels and genetic polymorphisms on clinical atherogenesis. This article aims to explain the mechanism in inhibiting the development of atherosclerosis and clinical effects of TFPI, and provide new ideas for the clinical researches and mechanism studies of atherothrombosis.

Endothelial cells are the main components of the heart, blood vessels, and lymphatic vessels, which play an important role in regulating the physiological functions of the cardiovascular system. Endothelial dysfunction is involved in a variety of acute and chronic cardiovascular diseases. As a special type of epithelial-mesenchymal transition (EMT), endothelium to mesenchymal transition (EndMT) regulates the transformation of endothelial cells into mesenchymal cells accompanied by changes in the expression of various transcription factors and cytokines, which is closely related to vascular endothelial injury, vascular remodeling, myocardial fibrosis and valvar disease. Endothelial cells undergoing EndMT lose their endothelial characteristics and undergo a transition toward a more mesenchymal-like phenotype. However, the molecular mechanism of EndMT remains unclear. EndMT, as a type of endothelial dysfunction, can cause vascular remodeling which is a major determinant of atherosclerotic luminal area. Therefore, exploring the important signaling pathways in the process of EndMT may provide novel therapeutic strategies for treating atherosclerotic diseases.

Hydrogen sulfide (H2S) is an endogenous gaseous signaling molecule that plays important roles in the cardiovascular system. In our previous studies, we demonstrated that H2S regulates lipid metabolism. In the present study, we aimed to explore the mechanisms through which H2S regulates lipid metabolism in HepG2 cells in vitro. Treatment of the HepG2 cells with H2S inhibited the expression of proprotein convertase subtilisin/kexin type 9 (PCSK9) and increased the level of low‑density lipoprotein receptor (LDLR) in a time‑ and dose‑dependent manner. The knockdown of PCSK9 by siRNA effectively increased the levels of LDLR and 1,1'‑dioctadecyl‑3,3,3',3'‑tetramethyl‑indocarbocyanine perchlorate‑labeled LDL (DiI‑LDL) uptake in the H2S‑treated HepG2 cells. Furthermore, the phosphoinositide 3‑kinase (PI3K)/protein kinase B (Akt)‑sterol regulatory element binding proteins 2 (SREBP‑2) signaling pathway was confirmed to be involved in H2S‑regulated PCSK9 expression. Notably, the HepG2 cells were incubated with 30% serum and DiI‑LDL for 24 h, and the results revealed that H2S increased lipid uptake, but caused no increase in lipid accumulation. On the whole, the findings of this study demonstrate that H2S is involved in the regulation of lipid metabolism in HepG2 cells through the regulation of the expression of PCSK9 via the PI3K/Akt‑SREBP‑2 signaling pathway. To the very best of our knowledge, this study is the first to report that H2S can regulate the expression of PCSK9.

Cystatin C (CysC)-induced autophagy may play a beneficial role in preventing subarachnoid hemorrhage-induced cerebral vasospasm. The role of CysC in endothelial cells (ECs) autophagy is unknown. This study explores the role of CysC during the process of oxidative stress in human umbilical vein endothelial cells (HUVECs). Oxidized LDL (oxLDL) was used to stimulate HUVECs in vitro study. The lactate dehydrogenase (LDH) release and malondialdehyde (MDA) level were assayed. Western blot is used to detect the expression levels of LC3 and P62. The present study demonstrated that LDH release and MDA levels increased after oxLDL exposure, however, CysC and NAC (N-acetyl-cysteine) decreased LDH release and MDA levels induced by oxLDL. The difference was a statistically significant amount (P

Hydrogen sulfide (H2S) exerts an anti-atherosclerotic effect and decreases foam cell formation. Lipoprotein-associated phospholipase A2 (Lp-PLA2) is a key factor involved in foam cell formation. However, the association between H2S and Lp-PLA2 expression levels with respect to foam cell formation has not yet been elucidated. The present study investigated whether H2S can affect foam cell formation and potential signalling pathways via regulation of the expression and activity of Lp-PLA2. Using human monocytic THP-1 cells as a model system, it was observed that oxidized low-density lipoprotein (ox-LDL) not only upregulates the expression level and activity of Lp-PLA2, it also downregulates the expression level and activity of Cystathionine γ lyase. Exogenous supplementation of H2S decreased the expression and activity of Lp-PLA2 induced by ox-LDL. Moreover, ox-LDL induced the expression level and activity of Lp-PLA2 via activation of the p38MAPK signalling pathway. H2S blocked the expression levels and activity of Lp-PLA2 induced by ox-LDL via inhibition of the p38MAPK signalling pathway. Furthermore, H2S inhibited Lp-PLA2 activity by blocking the p38MAPK signaling pathway and significantly decreased lipid accumulation in ox-LDL-induced macrophages, as detected by Oil Red O staining. The results of the present study indicated that H2S inhibited ox-LDL-induced Lp-PLA2 expression levels and activity by blocking the p38MAPK signalling pathway, thereby improving foam cell formation. These findings may provide novel insights into the role of H2S intervention in the progression of atherosclerosis.

Atherosclerosis is a chronic arterial wall illness that forms atherosclerotic plaques within the arteries. Plaque formation and endothelial dysfunction are atherosclerosis' characteristics. It is believed that the occurrence and development of atherosclerosis mainly include endothelial cell damage, lipoprotein deposition, inflammation and fibrous cap formation, but its molecular mechanism has not been elucidated. Therefore, protecting the vascular endothelium from damage is one of the key factors against atherosclerosis. The factors and processes involved in vascular endothelial injury are complex. Finding out the key factors and mechanisms of atherosclerosis caused by vascular endothelial injury is an important target for reversing and preventing atherosclerosis. Changes in cell adhesion are the early characteristics of EndMT, and cell adhesion is related to vascular endothelial injury and atherosclerosis. Recent researches have exhibited that endothelial-mesenchymal transition (EndMT) can urge atherosclerosis' progress, and it is expected that inhibition of EndMT will be an object for anti-atherosclerosis. We speculate whether inhibition of EndMT can become an effective target for reversing atherosclerosis by improving cell adhesion changes and vascular endothelial injury. Studies have shown that H

Monocyte chemoattractant protein-1 induced protein 1 (MCPIP1), one of the MCPIP family members, is characterized by the presence of both C-x8-C-x5-C-x3-H (CCCH)- type zinc finger and PilT-N-terminal domains. As a potent regulator of innate immunity, MCPIP1 exerts anti-inflammatory effects through its ribonuclease (RNase) and deubiquitinating enzyme activities to degrade cytokine mRNAs and inhibit nuclear factor- kappa B (NF-κB), respectively. MCPIP1 is expressed not only in immune cells but also in many other cell types, including cardiomyocytes, vascular endothelial cells (ECs) and smooth muscle cells (SMCs). Increasing evidence indicates that MCPIP1 plays a role in the regulation of cardiac functions and is involved in the processes of vascular diseases, such as ischemia-reperfusion (I/R) and atherosclerosis. To better understand the emerging roles of MCPIP1 in the cardiovascular system, we reviewed the current literature with respect to MCPIP1 functions and discussed its association with the pathogenesis of cardiovascular diseases and the implication as a therapeutic target.

Circular RNAs (circRNAs) are a class of newly-identified non-coding RNA that lack 5’ (cap) and 3’ (polyadenylation) ends and are linked by a covalent bond to form a closed loop structure. In comparison to linear RNAs, circRNAs are more resistant to exonuclease RNase R-mediated degradation with a much stronger stability due to the absence of 3’ terminals. Consequently, the extraordinary nature of circRNAs enables it to be potentially used as a biomarker and gene targeting. Similarly, circRNAs can play a significant regulatory role in gene expression where it can indirectly regulate the expression of the downstream target genes of microRNAs (miRNAs) by miRNA sponges. The aim of this review is to highlight the function of circRNAs as well as their vital roles in the central nervous system (CNS) regulation and neurological diseases.

Proprotein convertase subtilisin/kexin 9 (PCSK9) is the ninth member of the secretory serine protease family. It binds to low-density lipoprotein receptor (LDLR) for endocytosis and lysosome degradation in the liver, resulting in an increasing in circulating LDL-cholesterol (LDL-c) level. Since a PCSK9 induced increase in plasma LDL-c contributes to atherosclerosis, PCSK9 inhibition has become a new strategy in preventing and treating atherosclerosis. However, in addition to the effect of PCSK9 on elevating blood LDL-c levels, accumulating evidence shows that PCSK9 plays an important role in inflammation, likely representing another major mechanism for PCSK9 to promote atherosclerosis. In this review, we discuss the association of PCSK9 and inflammation, and highlight the specific effects of PCSK9 on different vascular cellular components involved in the atherosclerotic inflammation. We also discuss the clinical evidence for the association between PCSK9 and inflammation in atherosclerotic cardiovascular disease. A better understanding of the direct association of PCSK9 with atherosclerotic inflammation might help establish a new role for PCSK9 in vascular biology and identify a novel molecular mechanism for PCSK9 therapy.

Atherosclerosis is characterized by chronic inflammation and lipid accumulation in arterial walls, resulting in several vascular events. Proprotein convertase subtilisin kexin 9 (PCSK9), a serine protease, has a pivotal role in the degradation of hepatic low-density lipoprotein receptor (LDLR). It can increase plasma concentrations of low-density lipoprotein cholesterol and affect lipid metabolism. Recently, PCSK9 has been found to accelerate atherosclerosis via mechanisms apart from that involving the degradation of LDLR, with an emerging role in regulating the inflammatory response in atherosclerosis. Apolipoprotein E receptor 2 (apoER2), one of the LDLR family members expressed in macrophages, can bind to its ligand apolipoprotein E (apoE), exhibiting an anti-inflammatory role in atherosclerosis. Evidence suggests that apoER2 is a target of PCSK9. This review aims to discuss PCSK9 as a potential regulator of apoE/apoER2 against inflammation in atherosclerosis.

Elevated plasma low-density lipoprotein cholesterol (LDL-C) is an important risk factor for cardiovascular diseases. Statins are the most widely used therapy for patients with hyperlipidemia. However, a significant residual cardiovascular risk remains in some patients even after maximally tolerated statin therapy. Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a new pharmacologically therapeutic target for decreasing LDL-C. PCSK9 reduces LDL intake from circulation by enhancing LDLR degradation and preventing LDLR recirculation to the cell surface. Moreover, PCSK9 inhibitors have been approved for patients with either familial hypercholesterolemia or atherosclerotic cardiovascular disease, who require additional reduction of LDL-C. In addition, PCSK9 inhibition combined with statins has been used as a new approach to help reduce LDL-C levels in patients with either statin intolerance or unattainable LDL goal. This review will discuss the emerging anti-PCSK9 therapies in the regulation of cholesterol metabolism and atherosclerosis.

The G protein-coupled receptor APJ and its cognate ligand, apelin, are widely expressed throughout human body. They are implicated in different key physiological processes such as angiogenesis, cardiovascular functions, fluid homeostasis, and energy metabolism regulation. Recently, a new endogenous peptidic ligand of APJ, named Elabela, has been identified and shown to play a crucial role in embryonic development. In addition, increasing evidences show that Elabela is also intimate associated with a large number of physiological processes in adulthood. However, a comprehensive summary of Elabela has not been reported to date. In this review, we provide an overview of the biological functions of Elabela. Collectively, Elabela, a potential therapeutic peptide, exerts diverse biological functions in both embryos and adult organisms, such as dysontogenesis, self-renewing of human embryonic stem cells, endoderm differentiation, heart morphogenesis, cardiac dyfunctions, blood pressure control, angiogenesis, blood pressure control, regulation of food and water intake, bone formation, and kidney diseases.

High concentrations of plasma lipoprotein(a) [Lp(a)] have been inferred to be an independent risk factor for cardiovascular and cerebrovascular diseases, such as coronary artery diseases, restenosis, and stroke. Apolipoprotein(a) [apo(a)] is one of the most important components of Lp(a) and contributes greatly to the increased concentration of plasma Lp(a). As a critical positive transacting factor of apo(a) gene, Ets1 has been proven as a target gene of several miRNAs, such as miR-193b, miR-125b-5p, miR-200b, miR-1, and miR-499. In this study, a series of experiments on miRNAs and relative miRNAs inhibitor delivered HepG2 cells were conducted, and two miRNAs that downregulate the apo(a) by targeting the 3'-UTR of Ets1 were identified. Results showed that apo(a) and Ets1 were differentially expressed in SMMC7721 and HepG2 cell lines. Meanwhile, apo(a) and Ets1 were inversely correlated with several hepatic endogenous miRNAs, such as miR-125b-5p, miR-23b-3p, miR-26a-5p, and miR-423-5p, which were predicted to bind to Ets1. Results show that miR-125b-5p and miR-23b-3p mimics could inhibit the synthesis of apo(a) by directly targeting Ets1 in HepG2, thereby reducing the plasma Lp (a) concentration.

Cardiovascular diseases are the leading cause of death and morbidity worldwide. Atherosclerotic cardiovascular disease (ASCVD) is affected by both environmental and genetic factors. Microenvironmental disorders of the human gut flora are associated with a variety of health problems, not only gastrointestinal diseases, such as inflammatory bowel disease, but also extralintestinal organs. Hydrogen sulfide (H2S) is the third gas signaling molecule other than nitric oxide and carbon monoxide. In the cardiovascular system, H2S plays important roles in the regulation of blood pressure, angiogenesis, smooth muscle cell proliferation and apoptosis, anti-oxidative stress, cardiac functions. This review is aiming to explore the potential role of gut microbiota in the development of atherosclerosis through hydrogen sulfide production as a novel therapeutic direction for atherosclerosis.

Atherosclerosis (AS) remains the leading cause for global cardiovascular disease morbidity and mortality, and a major cause of cardiopathy, myocardial infarction and peripheral vascular diseases. Macrophages serve a critical role in atherosclerotic plaque stabilization and rupture, and the selective removal of macrophages may be beneficial in improving plaque stability. Autophagy is a process of self‑feeding, during which cytoplasmic proteins or organelles are packaged into vesicles and fused with the lysosome to form an autophagosome. The newly formed autophagosome can degrade internalized proteins, and this process may be used to serve the metabolic and self‑renewal requirements of the cell. Autophagy serves an important role in maintaining cell homeostasis and promoting cell survival, and therefore an imbalance in autophagy is closely associated with multiple diseases.