Cardiovascular research · 2025
Protective functions of liver X receptor α on calcified aortic valve: involvement of regulating endoplasmic reticulum-mediated osteogenic differentiation.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод пока не подготовлен
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Zeng Lishan, Chen Xin, Kang Kai, Lin Yifei, Zhou Zhongxing, Chen Shuaijie, Huang Chunkai, Lin Qingqing, Wang Hongzhuang, Chen Longqing, Yan Liangliang, Qiu HanFan, Lin Jinxiu, Lin Xiaoyan, Chai Dajun
Аннотация
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 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 endoplasmic reticulum kinase/eukaryotic initiation factor 2/activating transcription factor 4 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.
METHODS AND RESULTS: Osteogenic stimulation was performed following which a substantial downregulation of LXRα was observed in human calcific aortic valves and 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 endoplasmic reticulum kinase/eukaryotic initiation factor 2/activating transcription factor 4 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.