Therapeutic targeting of autophagy in cardiovascular disease.
Therapeutic targeting of autophagy in cardiovascular disease.
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DOI：
10.1016/j.yjmcc.2015.11.019
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发表时间：
2016-06
影响因子：
5
通讯作者：
Hill JA
中科院分区：
文献类型：
--
作者：
Schiattarella GG;Hill JA
自噬是一种进化上古老的细胞内分解代谢过程，在应对各种压力时，维持细胞内的动态平衡是必要的。在有丝分裂后细胞的情况下，细胞替换不是一种选择，细胞质成分和细胞器的精细质量控制尤其关键。由于自噬通量在维持细胞健康中的普遍和关键作用，因此在多种疾病过程中观察到自噬过程的扰动也就不足为奇了。大量临床前证据表明，自噬在心血管疾病中是一把双刃剑，其作用方式要么是有益的，要么是不适应的，具体取决于具体情况。有鉴于此，心肌细胞和其他类型的心血管细胞的自噬机制被认为是一个潜在的治疗靶点。在这里，我们总结了目前关于自噬在心血管疾病中的双重功能的知识。我们继续分析最近的证据表明，自噬通量的滴定具有作为一种新的治疗策略的潜力。
Autophagy is an evolutionarily ancient process of intracellular catabolism necessary to preserve cellular homeostasis in response to a wide variety of stresses. In the case of post-mitotic cells, where cell replacement is not an option, finely tuned quality control of cytoplasmic constituents and organelles is especially critical. And due to the ubiquitous and critical role of autophagic flux in the maintenance of cell health, it comes as little surprise that perturbation of the autophagic process is observed in multiple disease processes. A large body of preclinical evidence suggests that autophagy is a double-edged sword in cardiovascular disease, acting in either beneficial or maladaptive ways, depending on the context. In light of this, the autophagic machinery in cardiomyocytes and other cardiovascular cell types has been proposed as a potential therapeutic target. Here, we summarize current knowledge regarding the dual functions of autophagy in cardiovascular disease. We go on to analyze recent evidence suggesting that titration of autophagic flux holds potential as a novel treatment strategy.