Lin Da-Wei, Jiang Yi-Wen, Wu Chen, Zhang Hao, Li Ying-Ze, Wang Yao-Sheng
Department of Cardiology, Xinhua Hospital affiliated with Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai, China.
Cardiovasc Drugs Ther. 2024 Dec 16. doi: 10.1007/s10557-024-07658-x.
Cardiovascular diseases, exacerbated by cardiac fibrosis, are the leading causes of mortality. We aimed to determine the role of quercetin (QU) in cardiac fibrosis and the underlying mechanism.
In this study, 8-week-old mice were subjected to either transverse aortic constriction (TAC) or sham surgery, then they were administered QU or saline. Thereafter, cardiac function and cardiac hypertrophy were accessed. In vitro, cardiac fibroblasts (CFs) were treated with angiotensin II (Ang II) with or without QU. Western blot, qPCR, EdU incorporation assay, and immunofluorescence staining analysis were used to investigate the molecular and cellular features.
For the TAC mouse model, cardiac fibrosis was alleviated by QU. The study revealed that the trans-differentiation and proliferation of CFs promoted by Ang II would be reversed by QU in vitro. Mechanistically, QU exerted the anti-fibrotic effect by regulating the SIRT3/TGF-β/Smad3 signaling pathway.
Quercetin protects against cardiac fibrosis by mediating the SIRT3 signaling pathway.
由心脏纤维化加剧的心血管疾病是主要的死亡原因。我们旨在确定槲皮素（QU）在心脏纤维化中的作用及其潜在机制。
在本研究中，对8周龄小鼠进行主动脉缩窄（TAC）或假手术，然后给予它们QU或生理盐水。此后，评估心脏功能和心脏肥大情况。在体外，用血管紧张素II（Ang II）处理心脏成纤维细胞（CFs），同时添加或不添加QU。采用蛋白质免疫印迹法、实时定量聚合酶链反应、5-乙炔基-2'-脱氧尿苷掺入法和免疫荧光染色分析来研究分子和细胞特征。
对于TAC小鼠模型，QU减轻了心脏纤维化。研究表明，体外实验中QU可逆转由Ang II促进的CFs转分化和增殖。从机制上讲，QU通过调节SIRT3/转化生长因子-β/ Smad3信号通路发挥抗纤维化作用。
槲皮素通过介导SIRT3信号通路预防心脏纤维化。
