The Importance of Autophagy in Cardioprotection
The Importance of Autophagy in Cardioprotection
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DOI：
10.1007/s40292-013-0029-9
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发表时间：
2013
影响因子：
3
通讯作者：
S. Sciarretta;Derek Yee;Varun Shenoy;Narayani Nagarajan;J. Sadoshima
中科院分区：
文献类型：
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作者：
S. Sciarretta;Derek Yee;Varun Shenoy;Narayani Nagarajan;J. Sadoshima
自噬是细胞内溶酶体介导的分解代谢过程，其中衰老或受损的蛋白质和细胞器被称为自噬体的双膜限制性囊泡隔离，然后被溶酶体降解。虽然自噬在不同病理状态中的作用是上下文依赖性的，但已经表明，在心脏缺血期间，自噬作为心脏保护性适应被上调。我们最近证明，Rheb是一种直接激活雷帕霉素机制靶点复合物1的小GTP结合蛋白，是心肌缺血期间自噬的关键调节因子。我们发现心脏Rheb/mTORC 1信号在肥胖和代谢综合征的缺血期间以失调的方式被激活。Rheb/mTORC 1通路的这种不受控制的激活导致自噬抑制和心肌对缺血耐受性的降低。该数据进一步支持了自噬作为心肌缺血期间的基本保护机制的相关性，并表明自噬的再激活，特别是通过抑制Rheb/mTORC 1信号传导，可能代表治疗患有急性心肌梗死的受试者，特别是受代谢紊乱影响的受试者的有希望的治疗选择。本文就自噬在心脏保护中的生物学意义作一综述。
Autophagy is an intracellular lysosomal-mediated catabolic process in which senescent or damaged proteins and organelles are sequestered by double membrane-limited vesicles called autophagosomes, and then degraded by lysosomes. While the role of autophagy in different pathological states is context-dependent, it has been shown that during cardiac ischemia, autophagy is upregulated as a cardioprotective adaptation. We recently demonstrated that Rheb, a small GTP-binding protein that directly activates the complex 1 of the mechanistic target of rapamycin, is a critical regulator of autophagy during cardiac ischemia. We found that cardiac Rheb/mTORC1 signaling is activated in a deregulated manner during ischemia in obesity and metabolic syndrome. This uncontrolled activation of the Rheb/mTORC1 pathway leads to autophagy inhibition and to a reduction of myocardial tolerance to ischemia. This data further supports the relevance of autophagy as a fundamental protective mechanism during myocardial ischemia and suggests that reactivation of autophagy, in particular through the inhibition of Rheb/mTORC1 signaling may represent a promising therapeutic option to treat subjects with an acute myocardial infarction, particularly those affected by metabolic derangements. This review will deal with the biological significance of autophagy in cardioprotection.