Institute for Cardiovascular Prevention (IPEK), Ludwig-Maximillians-Universität (LMU), D-80336 Munich, Germany.
German Center for Cardiovascular Research (DZHK), Partner Site Munich Heart Alliance, D-80336 Munich, Germany.
Cells. 2021 Mar 11;10(3):625. doi: 10.3390/cells10030625.
Atherosclerosis is a chronic inflammatory disease of the arterial vessel wall and underlies the development of cardiovascular diseases, such as myocardial infarction and ischemic stroke. As such, atherosclerosis stands as the leading cause of death and disability worldwide and intensive scientific efforts are made to investigate its complex pathophysiology, which involves the deregulation of crucial intracellular pathways and intricate interactions between diverse cell types. A growing body of evidence, including in vitro and in vivo studies involving cell-specific deletion of autophagy-related genes (ATGs), has unveiled the mechanistic relevance of cell-specific (endothelial, smooth-muscle, and myeloid cells) defective autophagy in the processes of atherogenesis. In this review, we underscore the recent insights on autophagy's cell-type-dependent role in atherosclerosis development and progression, featuring the relevance of canonical catabolic functions and emerging noncanonical mechanisms, and highlighting the potential therapeutic implications for prevention and treatment of atherosclerosis and its complications.
动脉粥样硬化是动脉血管壁的一种慢性炎症性疾病,是心肌梗死和缺血性中风等心血管疾病发展的基础。因此,动脉粥样硬化是全球死亡和残疾的主要原因,人们正在进行密集的科学研究,以探讨其复杂的病理生理学,其中涉及关键细胞内途径的失调和不同细胞类型之间的复杂相互作用。越来越多的证据,包括涉及细胞特异性自噬相关基因(ATGs)缺失的体外和体内研究,揭示了细胞特异性(内皮细胞、平滑肌细胞和髓样细胞)缺陷自噬在动脉粥样形成过程中的机制相关性。在这篇综述中,我们强调了自噬在动脉粥样硬化发展和进展中依赖细胞类型的作用的最新见解,突出了经典分解代谢功能和新兴非经典机制的相关性,并强调了预防和治疗动脉粥样硬化及其并发症的潜在治疗意义。