PARM1基因敲低通过PRKCH-MAPK信号通路减轻主动脉瓣钙化。
Knockdown of PARM1 Alleviates Aortic Valve Calcification via the PRKCH-MAPK Signaling Pathway.
作者信息
Hu Haochang, Zhu Xian, Chen Jinyong, Cao Naifang, Yang Shuangshuang, Xie Lan, Hu Wangxing, Cheng Si, Fang Juan, Qian Yi, Xu Dilin, Qian Ningjing, Zhou Dao, Lu Jin, Dai Hanyi, Xue Junhui, Zhu Wei, Wang Jian'an, Liu Xianbao
机构信息
Department of Cardiology, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China; State Key Laboratory of Transvascular Implantation Devices, Hangzhou, Zhejiang, China; Heart Regeneration and Repair Key Laboratory of Zhejiang Province, Hangzhou, Zhejiang, China.
Department of Cardiovascular Surgery, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
出版信息
JACC Basic Transl Sci. 2025 Aug;10(8):101260. doi: 10.1016/j.jacbts.2025.02.019. Epub 2025 May 28.
With the aging of the population, the prevalence of calcific aortic valve disease (CAVD) has increased yearly. However, effective means to delay or even reverse the progression of CAVD are still lacking. This study revealed that prostate androgen-regulated mucin-like protein 1 (PARM1) expression was significantly up-regulated in calcified aortic valve tissues. Functional investigations demonstrated that PARM1 knockdown effectively suppressed osteogenic differentiation of valvular interstitial cells (VICs) and mitigated pathological aortic valve calcification. Mechanically, PARM1 knockdown down-regulated PRKCH mRNA expression, consequently attenuating MAPK pathway activation during the osteogenic differentiation of VICs. In conclusion, PARM1 could be a feasible target for CAVD prevention.
随着人口老龄化，钙化性主动脉瓣疾病（CAVD）的患病率逐年上升。然而，仍缺乏有效延缓甚至逆转CAVD进展的手段。本研究显示，前列腺雄激素调节的粘蛋白样蛋白1（PARM1）在钙化主动脉瓣组织中的表达显著上调。功能研究表明，敲低PARM1可有效抑制瓣膜间质细胞（VICs）的成骨分化，并减轻病理性主动脉瓣钙化。机制上，敲低PARM1可下调PRKCH mRNA表达，从而减弱VICs成骨分化过程中的MAPK途径激活。总之，PARM1可能是预防CAVD的一个可行靶点。
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