MicroRNA-19b-1 reverses ischaemia-induced heart failure by inhibiting cardiomyocyte apoptosis and targeting Bcl2 l11/BIM
MicroRNA-19b-1 reverses ischaemia-induced heart failure by inhibiting cardiomyocyte apoptosis and targeting Bcl2 l11/BIM
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MicroRNA-19b-1 通过抑制心肌细胞凋亡和靶向 Bcl2 l11/BIM 来逆转缺血引起的心力衰竭。
DOI：
10.1007/s00380-018-01336-3
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发表时间：
2019-07-01
影响因子：
1.5
通讯作者：
Jin, Wei
中科院分区：
文献类型：
--
作者：
Yang, Wenbo;Han, Yanxin;Jin, Wei
缺血诱导心肌细胞凋亡，并导致心肌梗死后心脏功能丧失和心力衰竭。microRNA-19 b-1（miR-19 b-1）是miR-17/92簇的关键成员，在抑制细胞凋亡中起着至关重要的作用。然而，miR-19 b-1在缺血性心力衰竭中的作用仍然未知。在这项研究中，缺血导致心肌细胞凋亡和miR-19 b-1表达的抑制，而miR-19 b-1过表达抑制体内和体外缺血诱导的心肌细胞凋亡。此外，miR-19 b-1不仅能缩小梗死面积，还能改善心肌梗死后心力衰竭，包括左心室射血分数和容积负荷的改变。在机制上，miR-19-1靶向并下调Bcl-2家族的促凋亡基因Bcl 2l 11/BIM的mRNA和蛋白表达。总之，这些结果揭示了miR-19 b-1在缺血诱导的心力衰竭中的重要作用。
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.