Cardiovascular disease (CVD) is the leading cause of death worldwide, especially in developed countries, and atherosclerosis (AS) is the common pathological basis of many cardiovascular diseases (CVDs) such as coronary heart disease (CHD). The role of the gut microbiota in AS has begun to be appreciated in recent years. Trimethylamine N-oxide (TMAO), an important gut microbe-dependent metabolite, is generated from dietary choline, betaine, and L-carnitine. Multiple studies have suggested a correlation between plasma TMAO levels and the risk of AS. However, the mechanism underlying this relationship is still unclear. In this review, we discuss the TMAO-involved mechanisms of atherosclerotic CVD from the perspective of inflammation, inflammation-related immunity, cholesterol metabolism, and atherothrombosis. We also summarize available clinical studies on the role of TMAO in predicting prognostic outcomes, including major adverse cardiovascular events (MACE), in patients presenting with AS. Finally, since TMAO may be a novel therapeutic target for AS, several therapeutic strategies including drugs, dietary, etc. to lower TMAO levels that are currently being explored are also discussed.

The prevalence of metabolic diseases, including obesity, dyslipidemia, type 2 diabetes mellitus (T2DM), and non-alcoholic fatty liver disease (NAFLD), is a severe burden in human society owing to the ensuing high morbidity and mortality. Various factors linked to metabolic disorders, particularly environmental factors (such as diet and gut microbiota) and epigenetic modifications, contribute to the progression of metabolic diseases. Dietary components and habits regulate alterations in gut microbiota; in turn, microbiota-derived metabolites, such as short-chain fatty acids (SCFAs), are influenced by diet. Interestingly, diet-derived microbial metabolites appear to produce substrates and enzymatic regulators for epigenetic modifications (such as DNA methylation, histone modifications, and non-coding RNA expression). Epigenetic changes mediated by microbial metabolites participate in metabolic disorders via alterations in intestinal permeability, immune responses, inflammatory reactions, and insulin resistance. In addition, microbial metabolites can trigger inflammatory immune responses and microbiota dysbiosis by directly binding to G-protein-coupled receptors (GPCRs). Hence, diet-gut microbiota-epigenetics may play a role in metabolic diseases. However, their complex relationships with metabolic diseases remain largely unknown and require further investigation. This review aimed to elaborate on the interactions among diet, gut microbiota, and epigenetics to uncover the mechanisms and therapeutics of metabolic diseases.

Copper is an essential micronutrient that plays a pivotal role in numerous physiological processes in virtually all cell types. Nevertheless, the dysregulation of copper homeostasis, whether towards excess or deficiency, can lead to pathological alterations, such as atherosclerosis. With the advent of the concept of copper-induced cell death, termed cuproptosis, researchers have increasingly focused on the potential role of copper dyshomeostasis in atherosclerosis. In this review, we provide a broad overview of cellular and systemic copper metabolism. We then summarize the evidence linking copper dyshomeostasis to atherosclerosis and elucidate the potential mechanisms underlying atherosclerosis development in terms of both copper excess and copper deficiency. Furthermore, we discuss the evidence for and mechanisms of cuproptosis, discuss its interactions with other modes of cell death, and highlight the role of cuproptosis-related mitochondrial dysfunction in atherosclerosis. Finally, we explore the therapeutic strategy of targeting this novel form of cell death, aiming to provide some insights for the management of atherosclerosis.

Low-density lipoprotein cholesterol (LDL-C) plays an important role in the formation, incidence, and development of atherosclerosis (AS). Low-density lipoproteins can be divided into two categories: large and light LDL-C and small, dense low-density lipoprotein cholesterol (sdLDL-C). In recent years, an increasing number of studies have shown that sdLDL-C has a strong ability to cause AS because of its unique characteristics, such as having small-sized particles and low density. Therefore, this has become the focus of further research. However, the specific mechanisms regarding the involvement of sdLDL-C in AS have not been fully explained. This paper reviews the possible mechanisms of sdLDL-C in AS by reviewing relevant literature in recent years. It was found that sdLDL-C can increase the atherogenic effect by regulating the activity of gene networks, monocytes, and enzymes. This article also reviews the research progress on the effects of sdLDL-C on endothelial function, lipid metabolism, and inflammation; it also discusses its intervention effect. Diet, exercise, and other non-drug interventions can improve sdLDL-C levels. Further, drug interventions such as statins, fibrates, ezetimibe, and niacin have also been found to improve sdLDL-C levels.

Postprandial lipemia plays an important role in the formation, occurrence, and development of atherosclerosis, and it is closely related to coronary heart disease and other diseases involving endothelial dysfunction, oxidative stress, inflammation, and other mechanisms. Therefore, it has become a focus area for further research. The studies on postprandial lipemia mainly include TG, TRL, VLDL, CM, and remnant cholesterol. Diurnal triglyceride patterns and postprandial hyperlipidemia are very relevant and are now insufficiently covered. The possible mechanisms between postprandial lipemia and cardiovascular disease have been reviewed in this article by referring to relevant literature in recent years. The research progress on the effects of postprandial lipemia on endothelial function, oxidative stress, and inflammation is highlighted. The intervention of postprandial lipemia is discussed. Non-medicinal intervention such as diet and exercise improves postprandial lipemia. As medicinal intervention, statin, fibrate, ezetimibe, omega-3 fatty acids, and niacin have been found to improve postprandial lipid levels. Novel medications such as pemafibrate, PCSK9, and apoCIII inhibitors have been the focus of research in recent years. Gut microbiota is closely related to lipid metabolism, and some studies have indicated that intestinal microorganisms may affect lipid metabolism as environmental factors. Whether intervention of gut microbiota can reduce postprandial lipemia, and therefore against AS, may be worthy of further study.