2. Academic Validation
  3. Protective functions of liver X receptor α on calcified aortic valve: involvement of regulating endoplasmic reticulum-mediated osteogenic differentiation

Protective functions of liver X receptor α on calcified aortic valve: involvement of regulating endoplasmic reticulum-mediated osteogenic differentiation

  • Cardiovasc Res. 2025 Mar 15:cvaf044. doi: 10.1093/cvr/cvaf044.
Lishan Zeng 1 2,  Xin Chen 1 2,  Kai Kang 1 2,  Yifei Lin 1 2,  Zhongxing Zhou 1 2,  Shuaijie Chen 1 2,  Chunkai Huang 1 2,  Qingqing Lin 3,  Hongzhuang Wang 1 2,  Longqing Chen 1 2,  Liangliang Yan 4,  HanFan Qiu 4,  Jinxiu Lin 1 2,  Xiaoyan Lin 3,  Dajun Chai 1 2
Affiliations

Affiliations

  • 1 Cardiovascular Department, The First Affiliated Hospital, Fujian Medical University; Key Laboratory of Metabolic Heart Disease in Fujian Province; Clinical Research Centre of Metabolic Cardiovascular Disease in Fujian Province，Fuzhou 350005, China.
  • 2 Cardiovascular Department, National Regional Medical Center, Binhai Branch of the First Affiliated Hospital, Fujian Medical University, Fuzhou 350212, China.
  • 3 Echocardiological Department, the First Affiliated Hospital, Fujian Medical University；Fujian Institute of Hypertension, Fuzhou 350005, China.
  • 4 Cardiac surgery Department, the First Affiliated Hospital, Fujian Medical University, Fuzhou 350005, China.
PMID: 40088465 DOI: 10.1093/cvr/cvaf044
Abstract

Aims: Effective therapeutic drugs for calcific aortic valve disease (CAVD) are lacking, although its incidence has been increasing over the past decade, and is predicted to continue rising in the future. This study aimed to explore the role and potential mechanisms of liver X receptor α (LXRα) in CAVD, which offers a promising approach for treating CAVD.

Methods and results: Osteogenic stimulation was performed following which a substantial downregulation of LXRα was observed in human calcific aortic valves and in valvular interstitial cells. Further functional investigations revealed that silencing LXRα exacerbated calcification both in vitro and in vivo. We showed that LXRα suppressed the protein kinase R-like ER kinase (PERK)/eukaryotic initiation factor 2 (elF2α)/activating transcription factor 4 (ATF4) pathway, which controls endoplasmic reticulum stress (ERS) and promotes osteogenic differentiation thereby slowing the course of CAVD.

Conclusion: Our research offers fresh perspectives on how LXRα controls the pathophysiology of CAVD via regulating ERS. The findings suggest that targeting LXRα is a potential treatment strategy for treating aortic valve calcification.

Keywords

calcific aortic valve disease; endoplasmic reticulum stress; liver X receptor α; valvular interstitial cells.

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