Yang Wenbo, Han Yanxin, Yang Chendie, Chen Yanjia, Zhao Weilin, Su Xiuxiu, Yang Ke, Jin Wei
Department of Cardiology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No 197 Ruijin 2nd Road, Shanghai, 200025, People's Republic of China.
Institute of Cardiovascular Disease, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China.
Heart Vessels. 2019 Jul;34(7):1221-1229. doi: 10.1007/s00380-018-01336-3. Epub 2019 Jan 3.
Ischaemia induces cardiac apoptosis and leads to a loss of cardiac function and heart failure after myocardial infarction. MicroRNA-19b-1 (miR-19b-1), a key member of the miR-17/92 cluster, plays crucial roles in inhibiting apoptosis. However, the role of miR-19b-1 in ischaemia-induced heart failure remains unknown. In this study, ischaemia resulted in cardiac apoptosis and the suppression of miR-19b-1 expression, whereas miR-19b-1 overexpression inhibited ischaemia-induced cardiac apoptosis in vivo and in vitro. Moreover, miR-19b-1 not only attenuated the infarct size but also ameliorated heart failure after myocardial infarction, including the changes in the left ventricular ejection fraction and volume load. Mechanically, miR-19-1 targeted and downregulated the mRNA and protein expression of Bcl2l11/BIM, a pro-apoptotic gene of the Bcl-2 family. Together, these results revealed an essential role of miR-19b-1 in ischaemia-induced heart failure.
缺血会诱发心肌细胞凋亡，并在心肌梗死后导致心功能丧失和心力衰竭。微小RNA-19b-1（miR-19b-1）是miR-17/92簇的关键成员，在抑制细胞凋亡中起关键作用。然而，miR-19b-1在缺血性心力衰竭中的作用尚不清楚。在本研究中，缺血导致心肌细胞凋亡并抑制miR-19b-1的表达，而miR-19b-1过表达在体内和体外均抑制缺血诱导的心肌细胞凋亡。此外，miR-19b-1不仅减小了梗死面积，还改善了心肌梗死后的心力衰竭，包括左心室射血分数和容量负荷的变化。机制上，miR-19-1靶向并下调Bcl2l11/BIM（Bcl-2家族的促凋亡基因）的mRNA和蛋白表达。总之，这些结果揭示了miR-19b-1在缺血性心力衰竭中的重要作用。
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