Irisin ameliorates angiotensin II-induced cardiomyocyte apoptosis through autophagy
Irisin ameliorates angiotensin II-induced cardiomyocyte apoptosis through autophagy
复制标题
鸢尾素通过自噬改善血管紧张素 II 诱导的心肌细胞凋亡
DOI：
10.1002/jcp.28382
复制
发表时间：
2019-10-01
影响因子：
5.6
通讯作者：
Jiang, Wei
中科院分区：
文献类型：
--
作者：
Li, Ruli;Wang, Xiaoxiao;Jiang, Wei
心肌肥厚是导致心力衰竭和猝死的主要原因。但发病机制尚不清楚。血管紧张素II可能导致压力超负荷引起的心脏肥大。在血管紧张素II处理的心肌细胞，有一个更大的横截面积，更多的凋亡细胞，并减少鸢尾素的表达。在血管紧张素II诱导的损伤后，在心肌细胞中观察到P62，自噬通量指数以及LC 3 II的增加。令人惊讶的是，补充Irisin增加了LC 3 II的表达，降低了P62的表达，包括RFP-GFP-LC 3B腺病毒转染的结果，并减少了心肌细胞凋亡，同时，Irisin的保护作用被自噬抑制剂3-甲基腺嘌呤逆转。在动物实验中，过表达鸢尾素可减少心肌细胞凋亡，减轻压力超负荷引起的心肌肥大。上述结果表明，鸢尾素诱导保护性自噬，减轻心肌细胞凋亡信号通路，从而减少血管紧张素II诱导的心肌细胞凋亡损伤后。因此，增加鸢尾素的表达可能是改善心肌肥厚患者心功能和生活质量的新途径。
Cardiac hypertrophy is the main cause of heart failure and sudden death in patients. But the pathogenesis is unclear. Angiotensin II may contribute to cardiac hypertrophy in response to pressure overload. In angiotensin II-treated cardiomyocytes, there is a larger cross-sectional area, more apoptosis cells, and a reduction of irisin expression. An increase in P62, an autophagy flux index, as well as LC3II, were observed in cardiomyocytes after angiotensin II-induced injury. Surprisely, irisin supplementation increased LC3II expression and decreased P62 expression, consisted of results of RFP-GFP-LC3B adenovirus transfection, and reduced cardiomyocyte apoptosis, meanwhile, the protection of irisin was reversed by the autophagy inhibitor 3-methyladenine. In animal experiments, overexpression of irisin reduced cardiomyocyte apoptosis and alleviated myocardial hypertrophy caused by pressure overload. The above results indicate that irisin-induced protective autophagy and alleviated the apoptosis signaling pathway in cardiomyocytes, consequently reducing cardiomyocyte apoptosis after angiotensin II-induced injury. Hence, increasing irisin expression may be a new way to improve cardiac function and quality of life in patients with cardiac hypertrophy.