Department of Pharmacy, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan, People's Republic of China.
Department of State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, People's Republic of China.
J Cell Physiol. 2019 Aug;234(10):17578-17588. doi: 10.1002/jcp.28382. Epub 2019 Feb 21.
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.
心肌肥厚是心力衰竭和患者猝死的主要原因。但其发病机制尚不清楚。血管紧张素Ⅱ可能通过对压力超负荷的反应促进心肌肥厚。在血管紧张素Ⅱ处理的心肌细胞中,横截面积更大,凋亡细胞更多,鸢尾素表达减少。在血管紧张素Ⅱ诱导损伤后,观察到自噬通量指标 P62 和 LC3II 在心肌细胞中的增加。令人惊讶的是,鸢尾素的补充增加了 LC3II 的表达,减少了 P62 的表达,这与 RFP-GFP-LC3B 腺病毒转染的结果一致,并减少了心肌细胞凋亡,同时,自噬抑制剂 3-甲基腺嘌呤逆转了鸢尾素的保护作用。在动物实验中,过表达鸢尾素可减少心肌细胞凋亡,并减轻压力超负荷引起的心肌肥厚。上述结果表明,鸢尾素诱导的保护性自噬减轻了心肌细胞中的凋亡信号通路,从而减少了血管紧张素Ⅱ诱导损伤后的心肌细胞凋亡。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。