Morusin Alleviates Aortic Valve Calcification by Inhibiting Valve Interstitial Cell Senescence Through Ccnd1/Trim25/Nrf2 Axis

Author:

Liu Zongtao1,Wang Kan1,Jiang Chen1,Chen Yuqi1,Liu Fayuan1,Xie Minghui1,Yim Wai Yen1,Yao Dingyi1,Qian Xingyu1,Chen Shiqi1,Shi Jiawei1,Xu Kang23ORCID,Wang Yixuan14,Dong Nianguo14

Affiliation:

1. Department of Cardiovascular Surgery Union Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan 430022 China

2. Hubei Provincial Engineering Technology Research Center for Chinese Medicine Processing School of Pharmacy Hubei University of Chinese Medicine Wuhan 430065 China

3. Hubei Shizhen Laboratory Wuhan 430065 China

4. Key Laboratory of Organ Transplantation Ministry of Education NHC Key Laboratory of Organ Transplantation Key Laboratory of Organ Transplantation Chinese Academy of Medical Sciences Wuhan 430022 China

Abstract

AbstractThe senescence of aortic valve interstitial cells (VICs) plays a critical role in the progression of calcific aortic valve disease (CAVD). However, the precise mechanisms underlying the senescence of VICs remain unclear, demanding the identification of a novel target to mitigate this process. Previous studies have highlighted the anti‐aging potential of morusin. Thus, this study aimed to explore the therapeutic potential of morusin in CAVD. Cellular experiments reveal that morusin effectively suppresses cellular senescence and cause a shift toward osteogenic differentiation of VICs in vitro. Mechanistically, morusin activate the Nrf2‐mediated antiaging signaling pathway by downregulating CCND1 expression and aiding Keap1 degradation through Trim 25. This activation lead to the upregulated expression of antioxidant genes, thus reducing reactive oxygen species production and thereby preventing VIC osteogenic differentiation. In vivo experiments in ApoE−/− mice on a high‐fat Western diet demonstrate the positive effect of morusin in mitigating aortic valve calcification. These findings emphasize the antiaging properties of morusin and its potential as a therapeutic agent for CAVD.

Funder

National Natural Science Foundation of China

China Postdoctoral Science Foundation

Key Technologies Research and Development Program

Publisher

Wiley

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