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Epigallocatechin-3-Gallate Inhibits Atrial Fibrosis and Reduces the Occurrence and Maintenance of Atrial Fibrillation and its Possible Mechanisms

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Abstract

Background

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.

Methods

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.

Results

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.

Conclusion

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.

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Data Availability

The data sets generated and analyzed in the course of this study are available from the corresponding authors upon reasonable request.

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Funding

This work was funded by the Scientific Research Project of National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University (No. Z2018B19), and 1·3·5 project for disciplines of excellence–Clinical Research Incubation Project, West China Hospital, Sichuan University (No. 2019HXFH029), the Major Science and Technology Project of Sichuan Province, China (No. 2021YFS0121), and Technology innovation research and development project of Chengdu Science and Technology Bureau (No. 2019YF05-00183-SN), and the Science and Technology Project of Sichuan Province Health Commission, China (No. 21PJ035).

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Author notes

  1. Tao Li and Qi Tong contributed equally to this work.

Authors and Affiliations

  1. Department of Cardiovascular Surgery, West China Hospital, Sichuan University, Chengdu, China

    Tao Li, Qi Tong, Zhengjie Wang, Jie Cai, Ke Lin & Yongjun Qian

  2. West China Medical School /West China Hospital, Sichuan University, Chengdu, China

    Ziqi Yang & Yiren Sun

  3. Department of Clinical Medicine, Mudanjiang Medical University, Mudanjiang, Heilongjiang, China

    Qiyue Xu

  4. Department of Cardiology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China

    Yuan Lu

  5. Chinese Journal of Thoracic and Cardiovascular Surgery, West China Hospital Press, West China Hospital, Sichuan University, Chengdu, China

    Xuemei Liu

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  1. Tao Li
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Contributions

Tao Li: Conceptualization, Methodology, Investigation, Software, Validation, Data curation, Formal analysis, Writing – original draft, Visualization; Tong Qi: Conceptualization, Methodology, Validation, Data curation, Formal analysis, Writing – review & editing; Zhengjie Wang: Formal analysis, Resources, Writing – review & editing, Visualization; Ziqi Yang: Software, Resources, Writing – review & editing; Yiren Sun: Conduct animal experiments; Jie Cai: Data Collection; Qiyue Xu: Writing – review & editing; Yuan Lu: Writing – review & editing; Xuemei Liu: Statistical analysis; Ke Lin: Conceptualization, Writing – review & editing, Supervision, Project administration, Funding acquisition, Yongjun Qian: Conceptualization, Writing – review & editing, Supervision, Project administration, Funding acquisition. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Yongjun Qian.

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Li, T., Tong, Q., Wang, Z. et al. Epigallocatechin-3-Gallate Inhibits Atrial Fibrosis and Reduces the Occurrence and Maintenance of Atrial Fibrillation and its Possible Mechanisms. Cardiovasc Drugs Ther (2023). https://doi.org/10.1007/s10557-023-07447-y

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