Current Atherosclerosis Reports最新文献

Purpose of review: The purpose of this review is to provide an in-depth exploration of the role of microRNAs (miRNAs) in the pathogenesis of coronary artery disease (CAD). Specifically, the review focuses on how miRNAs influence endothelial dysfunction, smooth muscle cell activity, and inflammatory responses, all of which contribute to the development and progression of CAD. Additionally, the review highlights the potential of circulating miRNAs as non-invasive diagnostic biomarkers and discusses their therapeutic potential in managing CAD. However, challenges remain in translating miRNA research into clinical practice, particularly concerning delivery mechanisms, specificity, and off-target effects, which are critical to overcoming before widespread clinical application.

Recent findings: Recent research has identified over 50 miRNAs as critical regulators of vascular homeostasis and CAD progression, playing significant roles in atherosclerotic plaque development, endothelial cell senescence, and impaired vascular repair. Certain miRNAs have been found to influence inflammatory pathways within atherosclerotic plaques, contributing to plaque instability and rupture, which are key events in acute coronary syndromes (ACS), such as myocardial infarction (MI) and unstable angina (UA). Furthermore, circulating miRNAs have emerged as promising non-invasive biomarkers for early detection, risk assessment, and therapeutic targeting in CAD. This review underscores the importance of miRNAs in the pathophysiology of CAD, highlighting their roles in endothelial dysfunction, smooth muscle cell behavior, and inflammatory responses. By modulating these processes, miRNAs contribute to the progression of atherosclerosis and the onset of ACS. The potential of circulating miRNAs as diagnostic tools and therapeutic targets offers new avenues for improving the management and outcomes of CAD. The review aims to lay the groundwork for future research and the development of miRNA-based therapies that could transform the landscape of CAD treatment, reshaping current therapeutic approaches and significantly improving patient outcomes.

Purpose of review: This review outlines obstructive sleep apnea (OSA) associated atherosclerotic cardiovascular disease (ASCVD) risk and highlights emerging data suggestive of sex differences.

Recent findings: Females with OSA have greater hypertension risk, higher carotid intima-media thickness, elevated cardiac enzymes, and worse outcomes following ischemic cardiovascular events relative to males with OSA. Mechanistically, this parallels sex differences in nocturnal hypoxemia, immune cell activity, inflammation, and endothelial function which frequently coincide with low estrogen levels. OSA-associated ASCVD risk appears more pronounced in females than males. This could be attributable to sex differences in the etiology of OSA and resultant activation of pathophysiological mechanisms. However, more data are required to differentiate causality from epiphenomena and develop individualized therapies to mitigate ASCVD in patients with OSA.

Purpose of review: Decreased serum high-density-lipoprotein-cholesterol (HDL-C), HDL particles, and cell-cholesterol-efflux-capacity have all been associated with increased atherosclerotic cardiovascular disease (ASCVD) risk. Our goals are to summarize recent findings with regard to these topics.

Recent findings: Apolipoprotein (apo) A1 containing HDL particles have been characterized by two-dimensional gel electrophoresis and apoA1 immunoblotting and range from very small preβ-1 HDL, small α-4 HDL, medium α-3 HDL to large and very large α-2 and α-1 HDL. Preβ-1 HDL are most efficient in serving as acceptors of free cholesterol and phospholipid from cells via ATP binding cassette transporter A1, while α-2 and α-1 HDL are most efficient in delivering cholesteryl-ester to the liver via scavenger receptor-B1 or to triglyceride-rich lipoproteins (TRL) in exchange for triglycerides via cholesteryl ester transfer protein (CETP). Recent research on the relationships of the lipid and protein composition, function, metabolism and levels of HDL particles to ASCVD risk will be reviewed, as will advances in potential therapeutic options. HDL particles are by far the most abundant lipoproteins in plasma and contain 110 proteins involved in lipid metabolism and immune function. ApoA1, apoA2, and all lipid classes are found in all HDL particles. Low levels of large and very large α-HDL and increased levels of very small preβ-1 HDL have been associated with increased ASCVD risk. The best therapeutic options for ASCVD risk reduction in patients with low HDL-C is optimizing other risk factors including low-density-lipoprotein (LDL)-C, small-dense LDL-C, plasma-glucose, body-mass-index, blood pressure, and the promotion of smoking cessation.

Purpose of review: Coronary heart disease (CHD) is a major global threat to human health. This review summarizes the latest progress of metabolomics in CHD research, and provides insights into the pathogenesis and identify dependable biomarkers of CHD.

Recent findings: This review has summarized 303 metabolic indicators related to CHD, with a focus on 53 biomarkers, and highlighted the top 10 biomarkers with significant clinical value. The biosynthesis of unsaturated fatty acids, amino acids, and aminoacyl-tRNA, as well as amino acid metabolism, are linked to CHD pathogenesis. Amino acids and lipids play essential roles in understanding the onset and progression of CHD. This review provides a new perspective on enhancing our understanding of CHD pathogenesis and developing effective treatment interventions.

Purpose of review: Dyslipidemia can present as early as infancy however the prevalence and long-term outcomes are unclear. There is an unmet need for guidance in the evaluation and treatment approach in these patients. This review summarizes the pathophysiology of dyslipidemia in infants and toddlers and highlights potential treatment options.

Recent findings: Secondary factors unique to this population including prematurity and reliance on intravenous nutrition play a role in the pathophysiology of dyslipidemia, though primary genetic causes are also recognized. Severe hypertriglyceridemia poses a risk of acute pancreatitis in an already vulnerable population. Persistent dyslipidemia is a concern for future premature cardiovascular disease. Management of dyslipidemia is dependent on its etiology and severity. Primary and secondary causes should be considered and addressed. Although a variety of therapeutic agents are available in older children and adults, no approved therapies exist at this age, though off-label use of medications may be considered.

Purpose of review: Circular RNAs (circRNAs), a distinct class of long noncoding RNAs characterized by covalently closed-loop structures, have emerged as pivotal regulators of gene expression. Their stability, abundance, and cell-type specificity make them increasingly relevant in cardiovascular disease pathogenesis and clinical management. Atherosclerosis, a chronic inflammatory disorder of the arterial wall, underlies many cardiovascular and cerebrovascular events, including myocardial infarction and stroke. This review provides a comprehensive analysis of circRNAs' influence on the development and progression of atherosclerotic plaques.

Recent findings: The role of circRNAs in atherogenesis, where they may function as atheroprotective or atherogenic factors by modulating endothelial and smooth muscle cell functions, macrophage activity, lipid metabolism, and inflammatory signaling, has recently emerged. This review explores both experimental and in vivo findings on the functions of specific circRNAs and their involvement in cellular autophagy, apoptosis, oxidative stress, and vascular remodeling. Additionally, the diagnostic potential of circulating circRNAs as biomarkers for plaque instability and rupture has been investigated. Understanding circRNA-mediated regulatory networks may open new avenues for precision diagnostics and targeted therapies in atherosclerotic cardiovascular disease.

Purpose of review: To provide an overview of the current available evidence on the burden of cardiovascular diseases (CVD) among African migrants, including its risk factors, underlying mechanisms, and prevention and treatment efforts, while highlighting critical gaps in knowledge.

Recent findings: The CVD burden is high among most African migrant populations. Underlying mechanisms for the high CVD burden include various pre- and post-migration factors, genetics, and epigenetics. Studies increasingly show substantial variation in CVD burden among African migrants across factors such as country of origin, host country, reason for migration, duration of stay, sex, and age. This variation is also observed among CVD risk factors and requires tailored prevention and treatment efforts. To fill critical gaps in knowledge, future studies need to recruit among diverse African migrant populations, in various high-income countries, using standardized methodologies with a focus on longitudinal designs, and integrating lifestyle, sociocultural, environmental, and genetic factors.

Purpose of review: Plaque erosion is the second most frequent cause of acute coronary syndrome, yet the biological processes and biomarkers associated with erosion remain incompletely understood. This review aims to examine the current understanding of plaque erosion, with a focus on identifying potential biomarkers.

Recent findings: Recent studies have identified distinct pathophysiological characteristics associated with plaque erosion, including variations in inflammatory response and immune cell infiltration within the culprit lesions and thrombi. Additionally, differences in the expression patterns of specific molecules have been noted, suggesting unique underlying mechanisms that contribute to plaque erosion. Understanding the differential expression and role of immune cells and biomarkers in erosion may be crucial for developing targeted therapies. The identification of biomarkers may help in the early detection and treatment of erosion-prone plaques, potentially reducing the incidence of acute coronary events.

Purpose of review: Abdominal aortic aneurysm (AAA) is a life-threatening vascular disorder with high mortality upon rupture, yet effective pharmacotherapy remains lacking. This review synthesizes the pivotal roles of myeloid cells-key mediators of aortic inflammation and remodeling-in AAA pathogenesis, highlighting their therapeutic targeting potential.

Recent findings: Single-cell RNA sequencing has revealed myeloid diversity in AAA. Among these myeloid populations, macrophages (including interferon-responsive monocytes, pro- and anti-inflammatory subsets, and reparative populations) emerge as central regulators of AAA pathogenesis, influencing disease initiation, progression, and tissue repair processes. Neutrophils promote vascular injury via neutrophil extracellular traps, while dendritic cells bridge innate-adaptive immunity. Eosinophils and myeloid-derived suppressor cells exhibited protective effects by immunoregulation. Mechanistic studies identified transcriptional, metabolic, and epigenetic regulators of myeloid plasticity. Clonal hematopoiesis and trained immunity may serve as potential novel mechanisms of myeloid cells involved in AAA. These mechanistic insights have inspired therapeutic innovation, with nanoparticle-targeted myeloid cell therapies showing promising immunomodulatory effects in mitigating AAA progression. Myeloid cells play a pivotal role in AAA pathogenesis by driving inflammatory responses, extracellular matrix degradation, and maladaptive vascular remodeling. Their functional heterogeneity, encompassing both destructive and protective subsets, highlights the need for precisely targeted therapeutic approaches. While single-cell technologies have significantly advanced our understanding of myeloid diversity, clinical translation remains challenged by microenvironmental crosstalk and potential off-target effects. Future research should prioritize: (1) spatial multi-omics characterization of myeloid-vascular interactions, (2) development of precision therapies targeting clonal hematopoiesis-driven subpopulations, and (3) combinatorial strategies to reprogram pathogenic myeloid phenotypes. Addressing these critical gaps may lead to transformative therapies for aneurysm stabilization, ultimately fulfilling the urgent unmet needs in AAA clinical management.