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COMP Improves Ang-II-Induced Atrial Fibrillation via TGF-β Signaling Pathway

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Abstract

Cartilage oligomeric matrix protein (COMP) regulates transforming growth factor-β (TGF-β) signaling pathway, which has been proved to be associated with skin fibrosis and pulmonary fibrosis. Atrial fibrosis is a major factor of atrial fibrillation (AF). Nevertheless, the interaction between COMP and TGF-β as well as their role in AF remains undefined. The purpose of this study is to clarify the role of COMP in AF and explore its potential mechanism. The hub gene of AF was identified from two datasets using bioinformatics. Furthermore, it was verified by the downregulation of COMP in angiotensin-II (Ang-II)-induced AF in mice. Moreover, the effect on AF was examined using CCK8 assay, ELISA, and western blot. The involvement of TGF-β pathway was further discussed. The expression of COMP was the most significant among all these hub genes. Our experimental results revealed that the protein levels of TGF-β1, phosphorylated Smad2 (P-Smad2), and phosphorylated Smad3 (P-Smad3) were decreased after silencing COMP, which indicated that COMP knockdown could inhibit the activation of TGF-β pathway in AF cells. However, the phenomenon was reversed when the activator SRI was added. COMP acts as a major factor and can improve Ang-II-induced AF via TGF-β signaling pathway. Thus, our research enriches the understanding of the interaction between COMP and TGF-β in AF, and provides reference for the pathogenesis and diagnosis of AF.

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Data Availability

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Authors and Affiliations

  1. Department of Cardiovascular Surgery, The Affiliated Hospital of Guangdong Medical University, No. 57, Renmin Avenue South, Xiashan District, Zhangjian City, 524001, Guangdong Province, China

    XiaoBi Cai, Mingliang Li, Ying Zhong & Wenkun Yang

  2. Department of Cardiovascular and Thoracic Surgery, The Affiliated Hospital of Guangdong Medical University, No. 57, Renmin Avenue South, Xiashan District, Zhangjian City, 524001, Guangdong Province, China

    Zhu Liang

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XBC: conceptualization; formal analysis; methodology; writing—original draft; validation; resources; ML: data curation; investigation; software; writing—review & editing; YZ: formal analysis; resources; writing—review & editing; visualization; WY and ZL: methodology; project administration; supervision; writing—review & editing; validation; all authors have read and approved the manuscript.

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Cai, X., Li, M., Zhong, Y. et al. COMP Improves Ang-II-Induced Atrial Fibrillation via TGF-β Signaling Pathway. Cardiovasc Toxicol 23, 305–316 (2023). https://doi.org/10.1007/s12012-023-09799-1

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