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桑辛素通过 Ccnd1/Trim25/Nrf2 轴抑制心脏瓣膜间质细胞衰老缓解主动脉瓣钙化。

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

机构信息

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

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

出版信息

Adv Sci (Weinh). 2024 May;11(20):e2307319. doi: 10.1002/advs.202307319. Epub 2024 Mar 19.

DOI:10.1002/advs.202307319
PMID:38502885
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11132047/
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.

摘要

主动脉瓣间质细胞（VICs）衰老在钙化性主动脉瓣疾病（CAVD）的进展中起着关键作用。然而，VICs 衰老的确切机制仍不清楚，需要确定新的靶标来减轻这一过程。先前的研究强调了桑辛素的抗衰老潜力。因此，本研究旨在探讨桑辛素在 CAVD 中的治疗潜力。细胞实验表明，桑辛素能有效抑制细胞衰老，并促使 VICs 在体外向成骨分化。在机制上，桑辛素通过下调 CCND1 表达和通过 Trim 25 帮助 Keap1 降解来激活 Nrf2 介导的抗衰老信号通路。这种激活导致抗氧化基因的上调表达，从而减少活性氧的产生，从而防止 VIC 成骨分化。高脂西方饮食 ApoE 小鼠的体内实验证明了桑辛素在减轻主动脉瓣钙化方面的积极作用。这些发现强调了桑辛素的抗衰老特性及其作为 CAVD 治疗剂的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6aa7/11132047/30affe6f29ca/ADVS-11-2307319-g007.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6aa7/11132047/1da5a7b25278/ADVS-11-2307319-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6aa7/11132047/30affe6f29ca/ADVS-11-2307319-g007.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6aa7/11132047/d7860cd7da95/ADVS-11-2307319-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6aa7/11132047/001290afab12/ADVS-11-2307319-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6aa7/11132047/41e498c69fc2/ADVS-11-2307319-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6aa7/11132047/b04569bc10e1/ADVS-11-2307319-g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6aa7/11132047/6405ea080bd8/ADVS-11-2307319-g012.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6aa7/11132047/ada0a7e5c8d8/ADVS-11-2307319-g011.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6aa7/11132047/58ea93d2779a/ADVS-11-2307319-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6aa7/11132047/b36c9a9cb0bd/ADVS-11-2307319-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6aa7/11132047/1da5a7b25278/ADVS-11-2307319-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6aa7/11132047/30affe6f29ca/ADVS-11-2307319-g007.jpg

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