Current Atherosclerosis Reports最新文献

Purpose of review: Recent advances have underscored the importance of interactions between the gut microbiota, vascular system and brain in stroke pathogenesis. This review introduces the conceptual framework of the gut-brain-vascular axis and summarizes evidence on how microbiota affects neurovascular integrity and stroke outcomes via intricate immunological, metabolic and endothelial mechanisms.

Recent findings: Recent clinical and epidemiological studies have demonstrated that specific profiles of gut microbiota are associated with stroke severity and clinical outcomes. Dysfunction of the gut barrier integrity and the translocation of endotoxins can induce low-grade systemic inflammation, which is a common mechanism underlying both cerebrovascular events and atherogenesis. Furthermore, microbial metabolites such as trimethylamine-N-oxide (TMAO), short-chain fatty acids (SCFAs) and bile acids (BAs) have been shown to modulate endothelial function, platelet hyperactivation and blood-brain barrier (BBB) permeability. Advances in BBB modelling reveal how microbial signals contribute to neurovascular dysfunction. Glycocalyx disruption, marked by elevated syndecan-1 (SDC1), reflects endothelial injury and could be used as a stroke biomarker. Furthermore, altered tryptophan metabolism via the kynurenine pathway is a contributing factor to neuroinflammation, thereby establishing a link between gut dysbiosis and cerebrovascular pathology. Emerging evidence on the gut-brain-vascular axis indicates that preventing dysbiosis may reduce stroke risk, while post-stroke modulation of the microbiota could enhance recovery. The gut-brain-vascular axis provides a novel and integrative model linking gut microbiota disfunction to neurovascular and atherosclerotic disease. Understanding these interconnected pathways may inform future approaches to risk stratification and cerebrovascular disease prevention and treatment.

Purpose of review: The ability of the nervous system to sense cues from medium and large arteries is critical for maintaining vascular integrity and function. However, there is currently no evidence that atherosclerotic plaques of arteries other than arterioles are directly hard-wired by axons to transmit signals to the brain or that efferent axons from the brain gain access to plaques. Yet, studies in experimental mice have shown that the outer connective tissue coat of arteries, i.e. the adventitia, adopts sentinel functions to indirectly and faithfully connect plaques to the brain forming artery brain circuits (ABCs). This review focuses on the adventitia as a site that establishes powerful biological platforms in the form of highly innervated neuroimmune cardiovascular interfaces (NICIs) and shows that these interfaces impact atherosclerosis progression.

Recent findings: The discovery of several cardiovascular brain circuits over the last several years considerably expanded our understanding how neural circuits regulate artery and heart homeostasis and disease. These circuits release neurotransmitters to modify leukocyte trafficking, affect endothelial cells, control vascular smooth muscle cells (VSMCs) behavior, and regulate local inflammation. Moreover, vascular inflammation in turn reorganizes neural innervation in the adventitia suggesting that tripartite communication networks between the cardiovascular, the nervous and the immune systems impact disease progression. In atherosclerosis, the formation of artery tertiary lymphoid organs (ATLOs) represents a specific form of NICIs adjacent to atherosclerotic plaques. The ATLO-associated NICIs act as hubs to connect plaques to the brain via multisynaptic projections and receive signals from the brain to convey to the arteries. These insights reveal a previously underappreciated level of integration between neural, immune and vascular networks in the pathogenesis of cardiovascular diseases. In this review, we consider recent advances in neuroimmune and neurovascular interactions in atherosclerosis, with a particular focus on the mechanisms by which these pathways contribute to disease progression.

Purpose of review: To review anti-obesity pharmacotherapy options and data to guide use in liver and kidney transplant recipients.

Recent findings: The number of liver and kidney transplant recipients with obesity (BMI ≥ 30 kg/m²) and concurrent disorders continues to grow. Up to 40% of liver and 33% of kidney recipients have obesity at transplant. Post-transplant weight gain is multi-factorial and common. Additionally, obesity and weight gain lead to lower allograft survival, increased cardiovascular risk, and decreased patient survival. Despite the high-risk population, anti-obesity medication use has not been widely studied or used in transplant recipients. Nutrient-stimulated hormones (NuSH) medications (glucagon-like peptide-1 receptor [GLP-1] agonists and dual agonists (GLP-1 and glucose-dependent insulinotropic polypeptide [GIP] receptor agonists) are highly effective agents for obesity treatment and cardiovascular event risk reduction in the general population and have spurred interest in obesity management in the transplant community. Data from randomized, placebo-controlled trials and integration of obesity medication expertise into routine care for transplant recipients is key to ensure improvement in long-term graft and patient survival.

Purpose of review: This review summarizes the pharmacologic profiles, clinical trial evidence, and practical considerations for the use of first-generation obesity medications phentermine, orlistat, phentermine/topiramate extended-release, bupropion/naltrexone sustained-release, and liraglutide 3.0 mg. Understanding the mechanisms, benefits, and limitations of these agents is essential for delivering comprehensive cardiometabolic care.

Recent findings: First-generation obesity medications continue to play an important role in clinical practice. These agents can be highly effective in appropriately selected patients. While mean weight loss is less than newer incretin-based therapies, trial data demonstrate that a substantial proportion of individuals on first-generation agents achieve ≥ 10% total body weight loss. First-generation obesity medications represent a cost-effective, evidence-based component of comprehensive obesity care-and remain critical tools to address atherosclerosis and other cardiometabolic complications of obesity.

Purpose of the review: We aimed to summarize the pathogenic role of IL-6 in atherothrombosis and myocardial infarction (MI), with focus on novel pathogenic mechanisms and current IL-6 targeted therapy in clinical cohorts.

Recent findings: IL-6 plays a major role in the pathogenesis of cardiovascular disease interacting with aging- and metabolic-driven inflammation, two conditions with overlapping molecular mechanisms. A novel pathogenic mechanism in cardiovascular disease (CVD) is the interaction between IL-6 and clonal hematopoiesis of indeterminate potential, CHIP, that involve the ten-eleven translocation-2 gene, a molecule with role in epigenetics. Recent studies showed reduced inflammation, a reduction in Lp (a) and inhibitory effects on platelets by anti-IL-6 (ziltivekimab) therapy in patients at risk for CVD. Anti-IL-6 receptor therapy (tocilizumab) showed reduced inflammation and improved myocardial function in MI patients, involving reduced degranulation in neutrophils and modulation of monocytes. Studies with clinical endpoints are still lacking and there also a need for developing therapy that selectively block the harmful IL-6 trans-signaling. IL-6 plays an important and many-faceted role in atherothrombosis including MI and ischemic stroke, and the IL-6 system represent a promising but still evolving therapeutic approach. A comprehensive understanding of the complexity of IL-6 signaling is needed to improve such treatment strategies.

Purpose of review: This review aims to provide a comprehensive overview of emerging evidence supporting the protective effects of perivascular adipose tissue (PVAT) browning in the pathophysiology of thoracic aortic aneurysm (TAA).

Recent findings: PVAT is increasingly recognized as an active regulator of vascular homeostasis. During cardiovascular disease (CVD), PVAT undergoes a phenotypic shift from a protective brown/beige state to a dysfunctional white phenotype, contributing to vascular remodeling. Accumulating data supports beneficial effects of PVAT browning on key mechanisms involved in TAA development, including endothelial dysfunction, vascular smooth muscle cell phenotypic switching, adventitial remodeling and PVAT phenotypic shift. Studies highlight PRDM16 as a central regulator of PVAT browning, with its deficiency promoting PVAT dysfunction, adventitial fibrosis, and TAA formation. Strategies aimed at enhancing PVAT browning represent a promising therapeutic direction. However, significant gaps remain in our understanding of human PVAT biology, its interaction with the aortic wall, and the development of specific imaging tools or biomarkers. Further research is needed to clarify PVAT's role in TAA pathophysiology and to advance browning-based interventions.

Purpose of review: We attempt to provide a framework for cardiovascular risk assessment related to environmental pollutants to enhance awareness of risk posed by environmental risk factors and highlight approaches for risk intervention.

Recent findings: Indisputable links between environmental exposures and cardiovascular outcomes exist. Although many of these relationships are well studied, such as air pollution, evidence continues to emerge regarding others, including noise, light, the built environment, and temperature. When the totality of the impact from environmental exposures are considered under the paradigm of the exposome, their health impact and disease burden form a considerable part of mitigatable residual cardiovascular risk. This risk can be attenuated by policy and, to a lesser extent, individual level actions. By harnessing artificial intelligence, we can move to integrated risk exposure analysis and target those at the highest risk with interventions.