Current Atherosclerosis Reports最新文献

Purpose of review: To explore sex-specific dimensions of cardiovascular disease (CVD) by addressing key questions: (1) What is the true burden of CVD in women, and how does it compare with that in men across diverse populations? (2) Do risk factors for CVD differ between sexes in prevalence, biological impact, and prognostic significance? (3) Should we adopt sex-specific cardiovascular risk stratification tools to improve diagnostic precision in women? (4) Is there a need for earlier or more aggressive preventive strategies in women, particularly for those with sex-specific or predominant risk factors?

Recent findings: CVD remains the leading cause of morbidity and mortality among women worldwide. Despite advances in care, significant sex-based disparities persist in awareness, diagnosis, risk stratification, and treatment. Women often present with distinct biological and psychosocial risk factors that are underrecognized in standard assessments. Emerging data support the development of sex-specific tools and earlier interventions tailored to these differences. This review highlights the need for a more nuanced, sex-sensitive approach to CVD prevention and management. By reevaluating traditional risk frameworks and incorporating female-specific and underrecognized contributors, there is potential to improve outcomes and close the persistent care gap for women.

Purpose of review: Heterozygous Familial Hypercholesterolemia (HeFH) is among the most common genetic conditions worldwide that affects ~ 1 in 300 individuals. HeFH is characterized by increased levels of low-density lipoprotein cholesterol (LDL-C) and increased risk of coronary artery disease (CAD), but there is a wide spectrum of severity within the HeFH population. This variability in expression is incompletely explained by known risk factors. The purpose of this review is to discuss recent studies that have examined how polygenic risk can modulate the phenotypic expression of HeFH.

Recent findings: Over the past several years, polygenic risk scores (PRS) that summarize information about many genetic variants that influence various traits have been developed. This includes polygenic risk scores for levels of LDL-C and other lipid fractions, CAD, and various other cardio-metabolic traits. In some individuals with a clinical phenotype compatible with HeFH but in whom a pathogenic variant is not present, an elevated PRS for LDL-C may explain the hypercholesterolemia. Among individuals with monogenic HeFH, an elevated PRS for LDL-C or CAD can further exacerbate the clinical phenotype and increase the risk of cardiovascular events. Conversely, a low PRS for these traits can mask the presentation of HeFH by decreasing the clinical severity and thus lead to incomplete phenotypic penetrance of a pathogenic HeFH-causing variant. Although HeFH is a prototypical monogenic condition, recent studies have revealed how the genomic background, as reflected by PRSs, can further modulate the clinical phenotype up or down in severity, thus adding a previously unrecognized level of complexity to monogenic disease. Having identified PRSs that can alter the clinical trajectory of HeFH, the next challenge for the field will be to implement PRS testing into clinical practice to allow clinicians to tailor risk prediction and treatment approaches based on each individual's unique complement of genetic factors.

Purpose of review: This review summarizes current literature on the diagnosis and treatment of hypertension, highlights persistent disparities in care, and critically evaluates recent randomized controlled trials (RCTs) of renal denervation (RDN) to clarify its emerging role in hypertension management.

Recent findings: Despite decades of therapeutic advances, progress in hypertension control has plateaued, with significant under-treatment contributing to ongoing cardiovascular disease, particularly among women and minority populations. Given the limitations of pharmacologic therapy alone, there is growing interest in alternative, procedure-based strategies. RDN, using both radiofrequency and ultrasound modalities, has shown promise in recent RCTs as an adjunctive treatment option. Hypertension remains a leading cause of cardiovascular morbidity and mortality, with persistently poor control rates in high-risk groups despite available therapies. RDN has demonstrated efficacy in reducing blood pressure and is being integrated into clinical practice guidelines. However, its long-term impact, safety, and effectiveness in diverse and historically underrepresented populations require further study to ensure equitable implementation.

Purpose of review: This review explores current knowledge on the beneficial and detrimental roles of nitric oxide (NO) in vascular biology, with a particular focus on the emerging role of protein S-nitrosylation in the pathophysiology of atherosclerosis.

Recent findings: Major risk factors for atherosclerosis include hypercholesterolemia, low-density lipoprotein (LDL) oxidation, hyperglycemia, hyperhomocysteinemia, chronic inflammation, and obesity. Recent studies have shown that protein S-nitrosylation interacts with these risk factors, influencing atherogenesis either by promoting or inhibiting disease progression. Atherosclerosis is a chronic inflammatory disorder marked by the accumulation of plaques within arterial walls, arising from intricate interactions among endothelial cells, monocytes/macrophages, and vascular smooth muscle cells. Understanding the role of S-nitrosylation in regulating key cellular events-such as endothelial dysfunction, foam cell formation, and vascular smooth muscle cell proliferation-offers new insights into the molecular mechanisms underlying atherosclerosis. These insights may ultimately lead to the identification of novel therapeutic targets for cardiovascular disease.

Purpose of review: This review aims to provide a comprehensive overview of the interplay between cholesterol crystals (CCs), NLRP3 inflammasome activation, and the progression of atherosclerosis.

Recent findings: Emerging evidence highlights the critical role of CCs in enhancing plaque inflammation and instability, increasing the risk of rupture or erosion. Early studies focused on the mechanism of lysosomal damage induced by CCs, leading to the release of cathepsin B into the cytoplasm, which in turn triggers NLRP3 inflammasome activation. More recent studies suggest that the trafficking of cholesterol within macrophages activates NLRP3 via CaMKII/JNK signaling, and NLRP3 deubiquitylation. The activation of the complement system by CCs can also contribute to NLRP3 inflammasome activation via changes in mitochondrial energy metabolism and ROS production worsening atherosclerosis. CCs can aggravate atherosclerosis by triggering a complex interplay of pathways, including lysosomal damage, cholesterol trafficking to ER, and complement system activation, all of which converge on the activation of the NLRP3 inflammasome, driving plaque inflammation and instability.

Purpose of review: This review summarizes recent advances in the clinical applications of glucagon-like peptide-1 receptor agonists (GLP-1RAs) beyond their established role in glycemic control for type 2 diabetes (T2DM).

Recent findings: Originally developed for glycemic control in T2DM, glucagon-like peptide-1 receptor agonists (GLP-1RAs) are now being utilized for a range of additional diseases and conditions. Strong evidence supports their efficacy in inducing clinically meaningful weight loss in individuals with overweight or obesity. Further studies have demonstrated cardiovascular benefits, kidney-protective effects, and therapeutic potential in obesity-related conditions such as obstructive sleep apnea and metabolic-associated steatotic liver disease. Emerging data also suggest possible roles in treating substance use disorders, including alcohol and nicotine dependence, though findings remain preliminary and variable. Despite these promising developments, GLP-1RAs are associated with side effects and high costs, contributing to variability in patient access. The therapeutic scope of GLP-1 receptor agonists extends beyond diabetes to multiple other conditions. Broader adoption requires careful evaluation of safety, cost, and evidence for less-established indications.

Purpose of review: Cell-cell adhesion between leukocytes, platelets and endothelial cells plays a critical role in vascular inflammation and thrombus formation. This review aims at providing a comprehensive picture of the contribution of the immunoglobulin superfamily (IgSF) cell adhesion receptor Junctional Adhesion Molecule-A (JAM-A) to the process of atherosclerosis.

Recent findings: Proinflammatory and proatherogenic stimulation of endothelial cells results in redistribution of JAM-A from cell-cell junctions to the apical surface to promote monocyte adhesion and transmigration. Agonist-stimulation of platelets results in elevated surface levels of JAM-A concomitant with enhanced release of soluble JAM-A (sJAM-A). sJAM-A promotes platelet aggregation, thrombus formation, and platelet-monocyte aggregate formation. Elevated levels of sJAM-A correlate with recurrent myocardial infarction. JAM-A is expressed by several cell types implicated in atherogenesis, notably endothelial cells, platelets, and leukocytes. Proinflammatory and proatherogenic stimuli induce a redistribution of JAM-A within endothelial cells. Stimulated platelets release sJAM-A into the circulation. This review illustrates the role of JAM-A in atherogenesis and elaborates the underlying mechanisms.

Purpose of review: Atherosclerotic cardiovascular disease (ASCVD), influenced by elevated plasma low-density lipoprotein (LDL) and cholesterol levels, is important to various acute cardiovascular and cerebrovascular diseases, causing life-threatening deaths worldwide. Early intervention for atherosclerosis is both essential and beneficial. As members of a class of transcription factors, sterol regulatory element-binding proteins (SREBPs) regulate the expression of most genes involved in lipid metabolism. This review aimed to present three aspects of SREBP regulation in the Endoplasmic Reticulum (ER), Golgi apparatus, and nucleus after maturation. Different subcellular localizations play integral roles in regulating the maturation and activity of SREBPs. Moreover, several drugs that target SREBPs for the treatment of atherosclerosis are described, with the aim of exploring SREBPs as new targets for treating atherosclerosis.

Recent findings: There are three members of the SREBP family, namely, SREBP-1a, SREBP-1c, and SREBP-2, all of which have differing functions. SREBP-1a and SREBP-1c regulate the synthesis of fatty acids, while SREBP-2 regulates cholesterol metabolism. SREBPs combine with the SREBP Cleavage-Activating Protein (SCAPs) to form the SCAP/SREBP complex. This complex can bind to and is regulated by insulin-induced genes (INSIG), affecting endoplasmic reticulum (ER)-to-Golgi translocation. SREBPs are sheared by 1-site protease (S1P) and 2-site protease (S2P) in a regular sequence on arrival at the Golgi apparatus, and are processed, matured, and transported to the nucleus for action. The review focuses on how SREBPs, crucial regulators of cholesterol and fatty acid metabolism, are controlled at different cellular locations (ER, Golgi, Nucleus), and explores their potential as drug targets for treating atherosclerosis, a major global health threat driven by high LDL cholesterol.