Molecular mechanisms of autophagy in the cardiovascular system.
Molecular mechanisms of autophagy in the cardiovascular system.
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DOI：
10.1161/circresaha.114.303788
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发表时间：
2015-01-30
影响因子：
20.1
通讯作者：
Klionsky DJ
中科院分区：
文献类型：
--
作者：
Gatica D;Chiong M;Lavandero S;Klionsky DJ
自噬是由多种细胞内或细胞外刺激触发的分解代谢循环途径，从酵母到哺乳动物都是保守的。在自噬过程中，不同的胞液成分被双膜小泡和自噬小体包裹，这些小泡后来与溶酶体或液泡融合，以降解其货物。自噬的调节失调与包括心血管疾病在内的多种病理因素有关，心血管疾病是世界上主要的死亡原因。因此，人们对确定控制心血管对疾病相关应激反应的新机制非常感兴趣。首先在衰竭的心脏中描述，心血管系统内的自噬已经被广泛地描述为心肌细胞、心脏成纤维细胞、内皮细胞和血管平滑肌细胞。在所有情况下，最佳自噬活动的窗口似乎对维持心血管内稳态和功能至关重要；自噬通量水平过高或不足都可能导致心脏病的发病。在这里，我们回顾了控制自噬形成的分子机制，并分析了自噬和心血管疾病之间的联系。
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 in order 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 widely characterized in cardiomyocytes, cardiac fibroblasts, endothelial cells and vascular smooth muscle cells. In all cases, a window of optimal autophagic activity appears 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.