Up-regulation of miR-195 contributes to cardiac hypertrophy-induced arrhythmia by targeting calcium and potassium channels
Up-regulation of miR-195 contributes to cardiac hypertrophy-induced arrhythmia by targeting calcium and potassium channels
复制标题
miR-195 的上调通过靶向钙和钾通道导致心脏肥大诱导的心律失常
DOI：
10.1111/jcmm.15431
复制
发表时间：
2020-05-28
影响因子：
5.3
通讯作者：
Sun, Lihua
中科院分区：
文献类型：
--
作者：
Xuan, Lina;Zhu, Yanmeng;Sun, Lihua
已有研究证实miR-195在心肌肥厚中表达增加，生物信息学网站Targetscan软件预测显示miR-195可直接靶向CACNB 1、KCNJ 2和KCND 3调控Cav β 1、Kir2.1和Kv4.3蛋白表达。本研究的目的是证实miR-195在心肌肥大引起的心律失常中的作用。HF小鼠心肌Cav β 1、Kir2.1和Kv4.3蛋白水平降低。miR-195在乳鼠心肌细胞中过表达后，ANP、BNP和β-MHC的表达上调，miR-195抑制剂可逆转这一现象。miR-195的过表达降低了野生型（WT）小鼠的EF%和FS%的估计心脏功能。透射电镜显示，慢病毒过表达miR-195后，小鼠心肌组织超微结构受到损伤。miR-195过表达增加了WT小鼠心律失常诱导的可能性和心律失常的持续时间。慢病毒携带的Lenti-miR-195抑制剂可逆转TAC诱导的小鼠EF%和FS%下降、心律失常发生率增加和心律失常持续时间延长。经miR-195处理后，小鼠Cav β 1、Kir2.1和Kv4.3蛋白表达降低。结果分别在动物和细胞水平上一致。荧光素酶实验结果表明，miR-195可能直接靶向CACNB 1、KCNJ 2和KCND 3，调控Cav β 1、Kir2.1和Kv4.3蛋白的表达。MiR-195通过抑制Cav β 1、Kir2.1和Kv4.3参与由心脏肥大引起的心律失常。
Previous studies have confirmed that miR-195 expression is increased in cardiac hypertrophy, and the bioinformatics website predicted by Targetscan software shows that miR-195 can directly target CACNB1, KCNJ2 and KCND3 to regulate Cav beta 1, Kir2.1 and Kv4.3 proteins expression. The purpose of this study is to confirm the role of miR-195 in arrhythmia caused by cardiac hypertrophy. The protein levels of Cav beta 1, Kir2.1 and Kv4.3 in myocardium of HF mice were decreased. After miR-195 was overexpressed in neonatal mice cardiomyocytes, the expression of ANP, BNP and beta-MHC was up-regulated, and miR-195 inhibitor reversed this phenomenon. Overexpression of miR-195 reduced the estimated cardiac function of EF% and FS% in wild-type (WT) mice. Transmission electron microscopy showed that the ultrastructure of cardiac tissues was damaged after miR-195 overexpression by lentivirus in mice. miR-195 overexpression increased the likelihood of arrhythmia induction and duration of arrhythmia in WT mice. Lenti-miR-195 inhibitor carried by lentivirus can reverse the decreased EF% and FS%, the increased incidence of arrhythmia and prolonged duration of arrhythmia induced by TAC in mice. After miR-195 treatment, the protein expressions of Cav beta 1, Kir2.1 and Kv4.3 were decreased in mice. The results were consistent at animal and cellular levels, respectively. Luciferase assay results showed that miR-195 may directly target CACNB1, KCNJ2 and KCND3 to regulate the expression of Cav beta 1, Kir2.1 and Kv4.3 proteins. MiR-195 is involved in arrhythmia caused by cardiac hypertrophy by inhibiting Cav beta 1, Kir2.1 and Kv4.3.