Knockdown of PARM1 Alleviates Aortic Valve Calcification via the PRKCH-MAPK Signaling Pathway

IF 8.4 1区医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS

JACC: Basic to Translational Science Pub Date : 2025-08-01 DOI:10.1016/j.jacbts.2025.02.019

Haochang Hu PhD , Xian Zhu MD , Jinyong Chen PhD , Naifang Cao PhD , Shuangshuang Yang MD , Lan Xie PhD , Wangxing Hu PhD , Si Cheng PhD , Juan Fang MD , Yi Qian PhD , Dilin Xu PhD , Ningjing Qian MD , Dao Zhou MD , Jin Lu MD , Hanyi Dai MD , Junhui Xue PhD , Wei Zhu MD , Jian’an Wang MD, PhD , Xianbao Liu MD, PhD

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引用次数: 0

Abstract

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.

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PARM1基因敲低可通过PRKCH-MAPK信号通路缓解主动脉瓣钙化

随着人口的老龄化，主动脉瓣钙化病（CAVD）的发病率逐年上升。然而，延缓甚至逆转CAVD进展的有效手段仍然缺乏。本研究发现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表达显著上调。功能研究表明，PARM1基因敲低可有效抑制瓣膜间质细胞（VICs）的成骨分化，减轻病理性主动脉瓣钙化。机械上，PARM1敲低下调了PRKCH mRNA的表达，从而减弱了vic成骨分化过程中MAPK通路的激活。综上所述，PARM1可能是CAVD预防的可行靶点。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

JACC: Basic to Translational Science CARDIAC & CARDIOVASCULAR SYSTEMS-

CiteScore

14.20

自引率

1.00%

发文量

161

审稿时长

16 weeks

期刊介绍： JACC: Basic to Translational Science is an open access journal that is part of the renowned Journal of the American College of Cardiology (JACC). It focuses on advancing the field of Translational Cardiovascular Medicine and aims to accelerate the translation of new scientific discoveries into therapies that improve outcomes for patients with or at risk for Cardiovascular Disease. The journal covers thematic areas such as pre-clinical research, clinical trials, personalized medicine, novel drugs, devices, and biologics, proteomics, genomics, and metabolomics, as well as early phase clinical trial methodology.