Current Atherosclerosis Reports最新文献

Purpose of review: Emerging evidence supports the promise of precision nutritional approaches for cardiovascular disease (CVD) prevention. Here, we discuss current findings from precision nutrition trials and studies reporting substantial inter-individual variability in responses to diets and dietary components relevant to CVD outcomes. We highlight examples where early precision nutrition research already points to actionable intervention targets tailored to an individual's biology and lifestyle. Finally, we make the case for high-density lipoproteins (HDL) as a compelling next generation target for precision nutrition aimed at CVD prevention. HDL possesses complex structural features including diverse protein components, lipids, size distribution, extensive glycosylation, and interacts with the gut microbiome, all of which influence HDL's anti-inflammatory, antioxidant, and cholesterol efflux properties. Elucidating the nuances of HDL structure and function at an individual level may unlock personalized dietary and lifestyle strategies to optimize HDL-mediated atheroprotection and reduce CVD risk.

Recent findings: Recent human studies have demonstrated that HDL particles are key players in the reduction of CVD risk. Our review highlights the role of HDL and the importance of personalized therapeutic approaches to improve their potential for reducing CVD risk. Factors such as diet, genetics, glycosylation, and gut microbiome interactions can modulate HDL structure and function at the individual level. We emphasize that fractionating HDL into size-based subclasses and measuring particle concentration are necessary to understand HDL biology and for developing the next generation of diagnostics and biomarkers. These discoveries underscore the need to move beyond a one-size-fits-all approach to HDL management. Precision nutrition strategies that account for personalized metabolic, genetic, and lifestyle data hold promise for optimizing HDL therapies and function to mitigate CVD risk more potently. While human studies show HDL play a key role in reducing CVD risk, recent findings indicate that factors such as diet, genetics, glycosylation, and gut microbes modulate HDL function at the individual level, underscoring the need for precision nutrition strategies that account for personalized variability to optimize HDL's potential for mitigating CVD risk.

Purpose of review: It is clear from epidemiological studies that patients at high and very-high risk of atherosclerotic cardiovascular diseases (ASCVD) risk do not reach lipid guideline-recommended targets. Thus, fixed-dose combinations of statins/ezetimibe, bempedoic acid/ezetimibe and statins/fibrates may represent a further armamentarium in the field of lipid-lowering approaches in these individuals.

Recent findings: The combination therapy of moderate-intensity statin with ezetimibe is not inferior to high-intensity statin monotherapy in reducing cardiovascular outcomes. Drug discontinuation or dose reduction is inferior with fixed-dose combination. The fixed-dose combination of bempedoic acid with ezetimibe is superior to bempedoic acid in monotherapy in lowering LDL-C and in reducing high-sensitivity C-reactive protein concentrations. The combination fenofibrate with atorvastatin is superior to monotherapies in lowering triglycerides. Lipid-lowering fixed-dose combinations may guarantee a higher therapy adherence, representing a better approach to control plasma lipids and thus ameliorate ASCVD burden. Additional studies will define the advantages on cardiovascular outcomes in high and very high-risk patients.

Purpose of review: To provide an insight into the new pharmacological options for the treatment of severe hypertriglyceridemia (sHTG).

Recent findings: sHTG is difficult to treat. The majority of the traditional pharmacological agents available have limited success in both robustly decreasing triglyceride levels and/or in reducing the incidence of acute pancreatitis (AP), the most severe complication of sHTG. Therapeutic options with novel mechanisms of action have been developed, such as antisense oligonucleotides (ASO) and small interfering RNA (siRNA) targeting APOC3 and ANGPTL3. The review discusses also 2 abandoned drugs for sHTG treatment, evinacumab and vupanorsen. The ASO targeting APOC3, volanesorsen, is approved for use in patients with familial chylomicronemia syndrome (FCS) in Europe. Olezarsen, an N-acetylgalactosamine (GalNAc)-conjugated ASO with the same target, seems to have a better safety and efficacy profile. siRNA targeting APOC3 and ANGPTL3, namely ARO-APOC3 and ARO-ANG3, are also promising for the treatment of sHTG. However, the ultimate clinical goal of any sHTG treatment, the decrease in the risk of AP, has not been definitively achieved till now by any pharmacotherapy, either approved or in development.

Purpose of review: To investigate the effects of omega-3 fatty acids on flow-mediated dilatation (FMD) and carotid intima-media thickness (CIMT) and explore the factors influencing these effects.

Recent findings: FMD was significantly higher in the omega-3 fatty acid group compared to the control group (mean difference = 0.90%; p = 0.0003). In particular, the subgroup with CHD (both EPA + DHA < 1 g/day and ≥ 1 g/day) and the subgroup without CHD but with CHD risk factors (only EPA + DHA ≥ 1 g/day) showed significantly increased FMD after supplementation of omega-3 fatty acids. CIMT was not significantly different between the omega-3 fatty acid and control groups (standardized mean difference = -0.08; p = 0.26). Subgroup analysis of CHD patients was not conducted because of the limited number of studies. Intake of omega-3 fatty acids improved FMD in patients with CHD and patients with risk factors for CHD. Further research is needed on the effects of omega-3 fatty acids on CIMT.

Purpose of review: Acute coronary syndrome (ACS) and non-alcoholic fatty liver disease (NAFLD) are two clinically common disease entities that share numerous risk factors. This review aimed to discuss the impacts of NAFLD on ACS.

Recent findings: In an era of improved control of traditional risk factors, the substantial burden of cardiometabolic abnormalities has caused widespread concern. NAFLD is considered the hepatic component of metabolic syndrome, which can exert an impact on human health beyond the liver. Accumulating studies have demonstrated that NAFLD is closely related to cardiovascular disease, especially coronary artery disease. Interestingly, although recent data have suggested an association between NAFLD and the incidence and outcomes of ACS, the results are not consistent. In this review, we comprehensively summarized evidence and controversies regarding whether NAFLD is a contributor to either the development of ACS or worse outcomes in patients with ACS. The potential pathophysiological and molecular mechanisms involved in the impacts of NAFLD on ACS were also elucidated.

Purpose of review: This review aims to summarize the latest findings on mechanosensing in atherosclerosis, elucidating the molecular mechanisms, cellular players, and potential therapeutic targets.

Recent findings: Atherosclerosis, a chronic inflammatory disease characterized by the buildup of lipid-laden plaque within arterial walls, is a major contributor to cardiovascular disease-related mortality and morbidity. Interestingly, atherosclerosis predominantly occurs in arterial areas with curves and branches. In these regions, endothelial cells encounter irregular blood flow with distinctive low-intensity fluctuating shear stress. On the other hand, straight sections of arteries, subjected to a consistent flow and related high-intensity, one-way shear stress, are relatively safeguarded against atherosclerosis due to shear-dependent, disease-preventing endothelial cell reactions. In recent years, researchers have been investigating the role of mechanosensing in the development and progression of atherosclerosis. At the core of mechanosensing is the ability of various cells to sense and respond to biomechanical forces in their environment. In the context of atherosclerosis, endothelial cells, smooth muscle cells, and immune cells are subjected to various mechanical or physical stimuli, including shear stress, cyclic strain, and matrix stiffness. These mechanical cues play a crucial role in regulating cellular behavior and contribute to the pathophysiology of atherosclerosis. Accumulating evidence suggests that various mechanical or physical cues play a critical role in the development and promotion of atherosclerosis.

Purpose of review: Cardiovascular disease (CVD) is one of the top comorbidities associated with COVID-19-both pre- and post-infection. This review examines the relationships between COVID-19 infection and cardiovascular health, with a specific focus on diet as an important modifiable risk factor.

Recent findings: Pandemic era studies of individuals battling and recovering from COVID-19 infection suggest a strong link between metabolic diseases, such as CVD, and SARS-CoV-2 infection susceptibility and severity. Other studies also demonstrate how COVID-19 lockdown policies and quarantine recommendations led to drastic lifestyle changes associated with increased CVD risk, such as reduced physical activity and lower diet quality. At the same time, new research is emerging that plant-based diets, which have previously been associated with lower CVD risk, may lower COVID-19 infection rates and severity of symptoms. Diet, COVID-19, and CVD intersect through complex biological mechanisms and related behavioral factors evidenced by clinical trials and epidemiological studies. Diet may be a critical tool for modifying risk of communicable and non-communicable conditions in the post-pandemic world.

Purpose of review: The majority of leukocytes in advanced human atherosclerotic plaques are T-cells. T-cell subsets exert pro- or anti-atherogenic effects largely via the cytokines they secrete. T_regulatory cells (T_regs) are anti-inflammatory, but may lose these properties during atherosclerosis, proposed to be downstream of cholesterol accumulation. Aged T-cells also accumulate cholesterol. The effects of T-cell cholesterol accumulation on T-cell fate and atherosclerosis are not uniform.

Recent findings: T-cell cholesterol accumulation enhances differentiation into pro-atherogenic cytotoxic T-cells and boosts their killing capacity, depending on the localization and extent of cholesterol accumulation. Excessive cholesterol accumulation induces T-cell exhaustion or T-cell apoptosis, the latter decreasing atherosclerosis but impairing T-cell functionality in terms of killing capacity and proliferation. This may explain the compromised T-cell functionality in aged T-cells and T-cells from CVD patients. The extent of T-cell cholesterol accumulation and its cellular localization determine T-cell fate and downstream effects on atherosclerosis and T-cell functionality.

Purpose of review: The goal of this review is to highlight work identifying mechanisms driving hypercholesterolemia-mediated endothelial dysfunction. We specifically focus on cholesterol-protein interactions and address specific questions related to the impact of hypercholesterolemia on cellular cholesterol and vascular endothelial function. We describe key approaches used to determine the effects of cholesterol-protein interactions in mediating endothelial dysfunction under dyslipidemic conditions.

Recent findings: The benefits of removing the cholesterol surplus on endothelial function in models of hypercholesterolemia is clear. However, specific mechanisms driving cholesterol-induced endothelial dysfunction need to be determined. In this review, we detail the latest findings describing cholesterol-mediated endothelial dysfunction, highlighting our studies indicating that cholesterol suppresses endothelial Kir2.1 channels as a major underlying mechanism. The findings detailed in this review support the targeting of cholesterol-induced suppression of proteins in restoring endothelial function in dyslipidemic conditions. The identification of similar mechanisms regarding other cholesterol-endothelial protein interactions is warranted.

Purpose of review: Dyslipidemia is a common condition characterized by abnormal lipid levels in the blood, which can increase the risk of cardiovascular disease. Physical activity and participation in sports have been shown to have a positive impact on lipid profiles and reduce the risk of dyslipidemia. Additionally, regular physical activity can lead to weight loss and improved insulin sensitivity, both of which are associated with improved lipid profiles. This review aims to provide an overview on the utility of physical activity in the management of dyslipidemia.

Recent findings: Improvements in lipid profiles were observed across both short- and long-term durations of high-intensity interval training (HIIT) and moderate intensity interval training (MIIT). However, it seems that more significant improvements in lipid profiles can be achieved with longer periods of physical activity and more intense exercise regimens. Several studies have investigated the relationship between aerobic exercise and HDL cholesterol (HDL-C), and the results suggest that HDL-C levels are more responsive to aerobic exercise compared to LDL cholesterol (LDL-C) and triglycerides (TG). Although findings on the effect of aerobic exercise on LDL-C levels have been inconsistent, there may still be beneficial changes in LDL-C subfractions that could provide cardiovascular protection. One such subfraction is plasma Lp(a), which contains Apo(a). However, unlike other LDL subfractions, Lp(a) is determined by genetics and is not influenced by physical activity. Therefore, it cannot be improved through exercise. Exercise is commonly believed to lead to a decrease in plasma TG concentrations. However, it is important to note that the baseline TG level may play a crucial role in determining the effect of exercise on the TG response. Factors such as individual variability and metabolic differences can influence the response of TG levels to exercise. Overall, exercise plays a crucial role in improving lipid profiles and promoting cardiovascular health. In conclusion, sport can be considered a form of medicine for dyslipidemia. Regular physical activity and participation in sports can improve lipid profiles, reduce the risk of cardiovascular disease, and improve overall health. It is essential to incorporate exercise and a healthy lifestyle into one's daily routine to prevent and manage dyslipidemia effectively.