PPP1R12C 在心房动中促进心房低收缩性
Srikanth Perike1,2,3, Francisco J Gonzalez-Gonzalez1,2,3, Issam Abu-Taha4
1Division of Cardiology, Department of Medicine, College of Medicine (S.P., F.J.G.-G., K.S.L., A.A., A.E.C., A.S., J.G., S.-G.O., D. Darbar, B.M.W., M.D.M.), University of Illinois at Chicago.
Circulation research
|September 22, 2023
概括
在心房动 (AF) 中增加的PPP1R12C蛋白质通过去酸化MLC2a来降低心房收缩性. 这种分子机制有助于AF患者中风风险.
科学领域:
- 心脏病学 心脏病学
- 分子生物学分子生物学
- 生物化学 生物化学
背景情况:
- 心房动 (AF) 是最常见的心律失常,显著增加中风风险.
- 心房缺约性是已知的AF中风风险的贡献者,但其分子基础尚不清楚.
- 这项研究研究了PPP1R12C (蛋白质酸酶1调节子单元12C) 在AF相关的心房低收缩性中的作用.
研究的目的:
- 测试假设增加PPP1R12C表达会通过降低MLC2a (心房髓光链2) 酸化而导致心房低收缩性.
- 阐明AF中PPP1R12C,PP1 (蛋白酸酶1) 和MLC2a之间的分子机制.
主要方法:
- 来自AF患者和对照组的人类心房附属体组织的分析.
- 西方涂抹,共免疫沉和酸化研究,以评估蛋白质相互作用和修饰.
- 使用HL-1细胞和药理抑制剂的体外研究,以及与小鼠心脏特异性lentiviral PPP1R12C过度表达的体内研究.
主要成果:
- 与对照组相比,人类AF患者的PPP1R12C表达增加了2倍,MLC2a酸化减少了>40%.
- 在AF中观察到增加的PPP1R12C-PP1c和PPP1R12C-MLC2a结合.
- 患有PPP1R12C过度表达的小鼠表现出心房膨胀,心房功能减弱和显著更高的AF诱导性.
结论:
- 在AF患者中,PPP1R12C水平升高与心房收缩率降低相关.
- 在小鼠中,PPP1R12C过度表达导致MLC2a脱,心房收缩率降低,心房动脉敏感性增加.
- 通过MLC2a通过PP1调节瘤细胞功能是AF期间心房收缩的一个关键因素.
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