Gatica Damián, Chiong Mario, Lavandero Sergio, Klionsky Daniel J
From the Department of Molecular, Cellular and Developmental Biology, and Life Sciences Institute, University of Michigan, Ann Arbor (D.G., D.J.K.); Advanced Center for Chronic Diseases (ACCDiS) and Center for Molecular Studies of the Cell (CEMC), Faculty of Chemical and Pharmaceutical Sciences, Faculty of Medicine, University of Chile, Santiago, Chile (M.C., S.L.); and Department of Internal Medicine (Cardiology Division), University of Texas Southwestern Medical Center, Dallas (S.L.).
Circ Res. 2015 Jan 30;116(3):456-67. doi: 10.1161/CIRCRESAHA.114.303788.
Autophagy is a catabolic recycling pathway triggered by various intra- or extracellular stimuli that is conserved from yeast to mammals. During autophagy, diverse cytosolic constituents are enveloped by double-membrane vesicles, autophagosomes, which later fuse with lysosomes or the vacuole to degrade their cargo. Dysregulation in autophagy is associated with a diverse range of pathologies including cardiovascular disease, the leading cause of death in the world. As such, there is great interest in identifying novel mechanisms that govern the cardiovascular response to disease-related stress. First described in failing hearts, autophagy within the cardiovascular system has been characterized widely in cardiomyocytes, cardiac fibroblasts, endothelial cells, and vascular smooth muscle cells. In all cases, a window of optimal autophagic activity seems to be critical to the maintenance of cardiovascular homeostasis and function; excessive or insufficient levels of autophagic flux can each contribute to heart disease pathogenesis. Here, we review the molecular mechanisms that govern autophagosome formation and analyze the link between autophagy and cardiovascular disease.
自噬是一种分解代谢的循环途径，由各种细胞内或细胞外刺激触发，从酵母到哺乳动物都保守存在。在自噬过程中，各种胞质成分被双膜囊泡（自噬体）包裹，自噬体随后与溶酶体或液泡融合以降解其内容物。自噬失调与多种病理状况相关，包括心血管疾病，这是全球主要的死亡原因。因此，人们对确定调控心血管对疾病相关应激反应的新机制非常感兴趣。自噬最初在衰竭心脏中被描述，在心血管系统中，心肌细胞、心脏成纤维细胞、内皮细胞和血管平滑肌细胞中的自噬已得到广泛研究。在所有情况下，最佳自噬活性窗口似乎对维持心血管稳态和功能至关重要；自噬通量过高或过低都可能导致心脏病发病机制。在这里，我们综述了调控自噬体形成的分子机制，并分析了自噬与心血管疾病之间的联系。
