Wang Shanjie, Fan Yanhong, Feng Xinyu, Sun Chuang, Shi Zhaofeng, Li Tian, Lv Jianjun, Yang Zhi, Zhao Zhijing, Sun Dongdong
Department of Cardiology, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
Department of Cardiology, Tangdu Hospital, Fourth Military Medical University, Xi'an, China.
Biochem Biophys Res Commun. 2018 Jan 1;495(1):292-299. doi: 10.1016/j.bbrc.2017.11.041. Epub 2017 Nov 7.
Cardiomyocyte autophagy and apoptosis are crucial events underlying the development of cardiac abnormalities and dysfunction after myocardial infarction (MI). A better understanding of the cell signaling pathways involved in cardiac remodeling may support the development of new therapeutic strategies for the treatment of heart failure (HF) after MI.
A cardiac MI injury model was constructed by ligating the left anterior descending (LAD) coronary artery. Neonatal cardiomyocytes were isolated and cultured to investigate the mechanisms underlying the protective effects of nicorandil on MI-induced injury.
Nicorandil reduced cardiac enzyme release, mitigated left ventricular enlargement and cardiac dysfunction after MI, as evaluated by echocardiography and hemodynamic measurements. According to the results of the western blot analysis and immunofluorescence staining, nicorandil enhanced autophagic flux and reduced apoptosis in cardiomyocytes subjected to hypoxic injury. Interestingly, nicorandil increased Mst1 and p-Mst1 levels in cardiomyocytes subjected to MI injury. Mst1 knockout abolished the protective effects of nicorandil on cardiac remodeling and dysfunction after MI. Mst1 knockout also abolished the beneficial effects of nicorandil on cardiac enzyme release and cardiomyocyte autophagy and apoptosis.
Nicorandil alleviates post-MI cardiac dysfunction and remodeling. The mechanisms were associated with enhancing autophagy and inhibiting apoptosis through Mst1 inhibition.
心肌细胞自噬和凋亡是心肌梗死（MI）后心脏异常和功能障碍发展的关键事件。更好地理解参与心脏重塑的细胞信号通路可能有助于开发治疗MI后心力衰竭（HF）的新治疗策略。
通过结扎左冠状动脉前降支（LAD）构建心脏MI损伤模型。分离并培养新生心肌细胞，以研究尼可地尔对MI诱导损伤的保护作用机制。
通过超声心动图和血流动力学测量评估，尼可地尔减少了心肌酶释放，减轻了MI后的左心室扩大和心脏功能障碍。根据蛋白质印迹分析和免疫荧光染色结果，尼可地尔增强了缺氧损伤心肌细胞的自噬通量并减少了凋亡。有趣的是，尼可地尔增加了MI损伤心肌细胞中Mst1和p-Mst1的水平。Mst1基因敲除消除了尼可地尔对MI后心脏重塑和功能障碍的保护作用。Mst1基因敲除也消除了尼可地尔对心肌酶释放以及心肌细胞自噬和凋亡的有益作用。
尼可地尔减轻MI后心脏功能障碍和重塑。其机制与通过抑制Mst1增强自噬和抑制凋亡有关。
