Nature Reviews Cardiology最新文献

The extracellular matrix is an essential component and constitutes a dynamic microenvironment of the vessel wall with an indispensable role in vascular homeostasis and disease. From early development through to ageing, the vascular extracellular matrix undergoes various biochemical and biomechanical alterations in response to diverse environmental cues and exerts precise regulatory control over vessel remodelling. Advances in novel technologies that enable the comprehensive evaluation of extracellular matrix components and cell–matrix interactions have led to the emergence of therapeutic strategies that specifically target this fine-tuned network. In this Review, we explore various aspects of extracellular matrix biology in vascular development, disorders and ageing, emphasizing the effect of the extracellular matrix on disease initiation and progression. Additionally, we provide an overview of the potential therapeutic implications of targeting the extracellular matrix microenvironment in vascular diseases.

The presence of cholesterol crystals (CCs) in tissues was first described more than 100 years ago. CCs have a pathogenic role in various cardiovascular diseases, including myocardial infarction, aortic aneurysm and, most prominently, atherosclerosis. Although the underlying mechanisms and signalling pathways involved in CC formation are incompletely understood, numerous studies have highlighted the existence of CCs at various stages of atheroma progression. In this Review, we summarize the mechanisms underlying CC formation and the role of CCs in cardiovascular disease. In particular, we explore the established links between lipid metabolism across various cell types and the formation of CCs, with a focus on CC occurrence in the vasculature. We also discuss CC-induced inflammation as one of the pathogenic features of CCs in the atheroma. Finally, we summarize the therapeutic strategies aimed at reducing CC-mediated atherosclerotic burden, including approaches to inhibit CC formation in the vasculature or to mitigate the inflammatory response triggered by CCs. Addressing CC formation might emerge as a crucial component in our broader efforts to combat cardiovascular disease.

Heart failure (HF) remains a leading cause of mortality, responsible for 13% of all deaths worldwide. The prognosis for patients with HF is poor, with only a 50% survival rate within 5 years. A major challenge of ischaemia-driven HF is the loss of cardiomyocytes, compounded by the minimal regenerative capacity of the adult heart. To date, replacement of irreversibly damaged heart muscle can only be achieved by complete heart transplantation. In the past 20 years, cell therapy has emerged and evolved as a promising avenue for cardiac repair and regeneration. During this time, cell therapy for HF has encountered substantial barriers in both preclinical studies and clinical trials but the field continues to progress and evolve from lessons learned from such research. In this Review, we provide an overview of ongoing trials of cell-based and cell product-based therapies for the treatment of HF. Findings from these trials will facilitate the clinical translation of cardiac regenerative and reparative therapies not only by evaluating the safety and efficacy of specific cell-based therapeutics but also by establishing the feasibility of novel or underexplored treatment protocols such as repeated intravenous dosing, personalized patient selection based on pharmacogenomics, systemic versus intramural cell delivery, and epicardial engraftment of engineered tissue products.