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

Haochang Hu1, Xian Zhu2, Jinyong Chen1

  • 1Department 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.

Insights

Prostate androgen-regulated mucin-like protein 1 (PARM1) is elevated in calcific aortic valve disease (CAVD). Targeting PARM1 suppressed valve calcification by inhibiting osteogenic differentiation of valvular interstitial cells.

Area of Science:

  • Cardiovascular Biology
  • Molecular Medicine
  • Biomaterials Science

Background:

  • Calcific aortic valve disease (CAVD) prevalence increases with population aging.
  • Current treatments for CAVD lack methods to delay or reverse disease progression.
  • Valvular interstitial cells (VICs) play a critical role in CAVD pathogenesis.

Purpose of the Study:

  • To investigate the role of prostate androgen-regulated mucin-like protein 1 (PARM1) in CAVD.
  • To determine if PARM1 is a potential therapeutic target for CAVD.

Main Methods:

  • Analysis of PARM1 expression in human calcified aortic valve tissues.
  • In vitro studies involving PARM1 knockdown in VICs.
  • Investigation of downstream signaling pathways, including PRKCH mRNA and MAPK activation.

Main Results:

  • PARM1 expression was significantly upregulated in calcified aortic valve tissues.
  • PARM1 knockdown suppressed VIC osteogenic differentiation and mitigated aortic valve calcification.
  • PARM1 knockdown led to decreased PRKCH mRNA expression and attenuated MAPK pathway activation.

Conclusions:

  • PARM1 is a key mediator in the osteogenic differentiation of VICs and CAVD progression.
  • PARM1 represents a potential therapeutic target for preventing or treating CAVD.