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

Overview

Journal Adv Sci (Weinh)

Specialty Biomedical Engineering

Date 2024 Mar 19

PMID 38502885

Authors

Zongtao Liu

Kan Wang

Chen Jiang

Yuqi Chen

Fayuan Liu

Minghui Xie

Wai Yen Yim

Dingyi Yao

Xingyu Qian

Shiqi Chen

Jiawei Shi

Kang Xu

Yixuan Wang

Nianguo Dong

Affiliations

Soon will be listed here.

Abstract

The 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.

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

Liu Z, Wang K, Jiang C, Chen Y, Liu F, Xie M Adv Sci (Weinh). 2024; 11(20):e2307319.

PMID: 38502885 PMC: 11132047. DOI: 10.1002/advs.202307319.

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