Overexpression of microRNA-1 causes atrioventricular block in rodents.
Overexpression of microRNA-1 causes atrioventricular block in rodents.
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microRNA-1 过度表达导致啮齿类动物房室传导阻滞
DOI：
10.7150/ijbs.4630
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发表时间：
2013
影响因子：
9.2
通讯作者：
Shan H
中科院分区：
文献类型：
--
作者：
Zhang Y;Sun L;Zhang Y;Liang H;Li X;Cai R;Wang L;Du W;Zhang R;Li J;Wang Z;Ma N;Wang X;Du Z;Yang B;Gao X;Shan H
本研究旨在探讨在心肌缺血(MI)时，microRNAs(MiRNAs)是否参与房室传导阻滞(AVB)。本研究首次成功建立了心脏特异的miR-1转基因(TG)小鼠模型。实时荧光定量聚合酶链式反应检测MIR-1水平。采用全细胞膜片钳记录L钙电流(ICa，L)和内向整流钾电流(Ik1)。免疫印迹法检测细胞间隙连接蛋白43(Cx43)的表达。激光扫描共聚焦显微镜观察心肌细胞内钙离子浓度的变化。MiR-1Tg小鼠AVB的发生率高于野生型(WT)小鼠。与WT小鼠相比，MiR-1转基因小鼠的心室肌细胞ICa、L的归一化峰电流幅度明显降低。同样，miR-1TG小鼠的IK1电流密度低于WT小鼠。与WT小鼠相比，miR-1转基因小鼠心肌细胞收缩[Ca~(2+)]i显著降低，静息[Ca~(2+)]i显著升高，且Cx43蛋白表达下调。给予LNA修饰的AntimiR-1可逆转上述变化。MIR-1的过度表达可能导致心脏对AVB易感性的增加，这为我们对缺血性心律失常的分子机制提供了新的见解。
The present study was designed to investigate whether microRNAs (miRNAs) are involved in atrioventricular block (AVB) in the setting of myocardial ischemia (MI). A cardiac-specific miR-1 transgenic (Tg) mouse model was successfully established for the first time in this study using microinjection. miR-1 level was measured by real-time qRT-PCR. Whole-cell patch clamp was employed to record L-type calcium current (ICa,L) and inward rectifier K+ current (IK1). Expression of connexin 43 (Cx43) protein was determined by western blot analysis. Alternations of [Ca2+]i was detected by laser scanning confocal microscopy in ventricular myocytes. The incidence of AVB was higher in miR-1 Tg mice than that in wild-type (WT) mice. The normalized peak current amplitude of ICa,L was lower in ventricular myocytes from miR-1 Tg mice as compared with WT mice. Similarly, the current density of IK1 was decreased in miR-1 Tg mice than that in WT mice. Compared with WT mice, miR-1 Tg mice exhibited a significant decrease of the systolic [Ca2+]i in ventricular myocytes but a prominent increase of the resting [Ca2+]i. Moreover, Cx43 protein was downregulated in miR-1 Tg mice compared to that in WT mice. Administration of LNA-modified antimiR-1 reversed all the above changes. miR-1 overexpression may contribute to the increased susceptibility of the heart to AVB, which provides us novel insights into the molecular mechanisms underlying ischemic cardiac arrhythmias.
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DOI：
10.1073/pnas.0509535102
发表时间：
2005-12-27
影响因子：
11.1
作者：
Kwon, C;Han, Z;Srivastava, D
通讯作者：
Srivastava, D
影响因子：
82.9
作者：
Yang, Baofeng;Lin, Huixian;Wang, Zhiguo
通讯作者：
Wang, Zhiguo
影响因子：
6
作者：
Peters, NS
通讯作者：
Peters, NS
影响因子：
3.6
作者：
Boutjdir, M;Chen, L;Buyon, JP
通讯作者：
Buyon, JP
DOI：
10.1111/j.1540-8167.1995.tb00357.x
发表时间：
1995-10-01
影响因子：
2.7
作者：
DAVIS, LM;RODEFELD, ME;SAFFITZ, JE
通讯作者：
SAFFITZ, JE