Department of Cardiovascular Surgery, West China Hospital, Sichuan University, Chengdu, China.
West China Medical School /West China Hospital, Sichuan University, Chengdu, China.
Cardiovasc Drugs Ther. 2024 Oct;38(5):895-916. doi: 10.1007/s10557-023-07447-y. Epub 2023 Mar 31.
Atrial fibrosis is one of the main causes of the onset and recurrence of atrial fibrillation (AF), for which there is no effective treatment. The aim of this study was to investigate the effect and mechanism of epigallocatechin-3-gallate (EGCG) on AF in rats.
The rat model of AF was established by rapid pacing induction after angiotensin-II (Ang-II) induced atrial fibrosis to verify the relationship between atrial fibrosis and the AF. The expression levels of TGF-β/Smad3 pathway molecules and lysyl oxidase (LOX) in AF were detected. Subsequently, EGCG was used to intervene Ang-II-induced atrial fibrosis to explore the role of EGCG in the treatment of AF and its inhibitory mechanism on fibrosis. It was further verified that EGCG inhibited the production of collagen and the expression of LOX through the TGF-β/Smad3 pathway at the cellular level.
The results showed that the induction rate and maintenance time of AF in rats increased with the increase of the degree of atrial fibrosis. Meanwhile, the expressions of Col I, Col III, molecules related to TGF-β/Smad3 pathway, and LOX increased significantly in the atrial tissues of rats in the Ang-II induced group. EGCG could reduce the occurrence and maintenance time of AF by inhibiting the degree of Ang-induced rat atrial fibrosis. Cell experiments confirmed that EGCG could reduce the synthesis of collagen and the expression of LOX in cardiac fibroblast induced by Ang-II. The possible mechanism is to down-regulate the expression of genes and proteins related to the TGF-β/Smad3 pathway.
EGCG could downregulate the expression levels of collagen and LOX by inhibiting the TGF-β/Smad3 signaling pathway, alleviating Ang-II-induced atrial fibrosis, which in turn inhibited the occurrence and curtailed the duration of AF.
心房纤维化是心房颤动（AF）发生和复发的主要原因之一，目前尚无有效的治疗方法。本研究旨在探讨表没食子儿茶素没食子酸酯（EGCG）对大鼠 AF 的作用及其机制。
通过血管紧张素Ⅱ（Ang-II）诱导的心房纤维化后快速起搏诱导建立大鼠 AF 模型，验证心房纤维化与 AF 的关系。检测 AF 中 TGF-β/Smad3 通路分子和赖氨酰氧化酶（LOX）的表达水平。随后，用 EGCG 干预 Ang-II 诱导的心房纤维化，探讨 EGCG 在 AF 治疗中的作用及其对纤维化的抑制机制。进一步在细胞水平上验证 EGCG 通过 TGF-β/Smad3 通路抑制胶原的产生和 LOX 的表达。
结果表明，随着心房纤维化程度的增加，大鼠 AF 的诱导率和维持时间增加。同时，Ang-II 诱导组大鼠心房组织中 Col I、Col III、TGF-β/Smad3 通路相关分子和 LOX 的表达明显增加。EGCG 可通过抑制 Ang 诱导的大鼠心房纤维化程度，降低 AF 的发生和维持时间。细胞实验证实，EGCG 可降低 Ang-II 诱导的心肌成纤维细胞胶原合成和 LOX 的表达。其可能的机制是下调 TGF-β/Smad3 通路相关基因和蛋白的表达。
EGCG 通过抑制 TGF-β/Smad3 信号通路下调胶原和 LOX 的表达，减轻 Ang-II 诱导的心房纤维化，进而抑制 AF 的发生并缩短其持续时间。
