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Canadian Journal of Cardiology

T cell Mineralocorticoid Receptor Deficiency Attenuates Pathological Ventricular Remodeling After Myocardial Infarction

  • Author Footnotes
    4 These authors contributed equally to this article.
    Yong-Li Wang
    Footnotes
    4 These authors contributed equally to this article.
    Affiliations
    Department of Cardiology, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, China

    National Center for Stomatology; National Clinical Research Center for Oral Diseases; Shanghai Key Laboratory of Stomatology, Shanghai 200011, China
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  • Author Footnotes
    4 These authors contributed equally to this article.
    Xiao-Xin Ma
    Footnotes
    4 These authors contributed equally to this article.
    Affiliations
    Laboratory of Oral Microbiota and Systemic Diseases, Shanghai Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai 200125, China

    National Center for Stomatology; National Clinical Research Center for Oral Diseases; Shanghai Key Laboratory of Stomatology, Shanghai 200011, China
    Search for articles by this author
  • Author Footnotes
    4 These authors contributed equally to this article.
    Hong Zhu
    Footnotes
    4 These authors contributed equally to this article.
    Affiliations
    Laboratory of Oral Microbiota and Systemic Diseases, Shanghai Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai 200125, China

    National Center for Stomatology; National Clinical Research Center for Oral Diseases; Shanghai Key Laboratory of Stomatology, Shanghai 200011, China
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  • Lan Bai
    Affiliations
    Laboratory of Oral Microbiota and Systemic Diseases, Shanghai Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai 200125, China

    National Center for Stomatology; National Clinical Research Center for Oral Diseases; Shanghai Key Laboratory of Stomatology, Shanghai 200011, China
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  • Lin-Juan Du
    Affiliations
    Laboratory of Oral Microbiota and Systemic Diseases, Shanghai Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai 200125, China

    National Center for Stomatology; National Clinical Research Center for Oral Diseases; Shanghai Key Laboratory of Stomatology, Shanghai 200011, China
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  • Shi-Wei Zhu
    Affiliations
    Department of Cardiology, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, China
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  • Yi-Tong Pan
    Affiliations
    Department of Cardiology, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, China
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  • Wen-Zhen Lin
    Affiliations
    Laboratory of Oral Microbiota and Systemic Diseases, Shanghai Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai 200125, China

    National Center for Stomatology; National Clinical Research Center for Oral Diseases; Shanghai Key Laboratory of Stomatology, Shanghai 200011, China
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  • Yuan Liu
    Affiliations
    Laboratory of Oral Microbiota and Systemic Diseases, Shanghai Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai 200125, China

    National Center for Stomatology; National Clinical Research Center for Oral Diseases; Shanghai Key Laboratory of Stomatology, Shanghai 200011, China
    Search for articles by this author
  • Yan Liu
    Affiliations
    Laboratory of Oral Microbiota and Systemic Diseases, Shanghai Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai 200125, China

    National Center for Stomatology; National Clinical Research Center for Oral Diseases; Shanghai Key Laboratory of Stomatology, Shanghai 200011, China
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  • Wei-wei Zhang
    Affiliations
    Department of Cardiology, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, China
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  • Xu-Min Hou
    Affiliations
    Department of Cardiology, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, China
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  • Ruo-Gu Li
    Correspondence
    Correspondence to: Ruo-Gu Li, MD, PhD. Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, 241 West Huaihai Road, Shanghai 200030, China. Phone: 86-21-62821990;
    Affiliations
    Department of Cardiology, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, China
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  • Sheng-Zhong Duan
    Correspondence
    Correspondence to: Sheng-Zhong Duan, MD, PhD. Shanghai Ninth People's Hospital Research Center, Shanghai Jiao Tong University School of Medicine, 115 Jinzun Rd, Shanghai 200125, China. Phone: 86-21-38452653; Fax: 86-21-63136856,
    Affiliations
    Laboratory of Oral Microbiota and Systemic Diseases, Shanghai Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai 200125, China

    National Center for Stomatology; National Clinical Research Center for Oral Diseases; Shanghai Key Laboratory of Stomatology, Shanghai 200011, China
    Search for articles by this author
  • Author Footnotes
    4 These authors contributed equally to this article.
Published:January 17, 2023DOI:https://doi.org/10.1016/j.cjca.2023.01.013

      Abstract

      Background

      Mineralocorticoid receptor (MR) antagonists have been widely used to treat heart failure (HF). Studies have shown that MR in T cells plays important roles in hypertension and myocardial hypertrophy. However, the function of T cell MR in myocardial infarction (MI) has not been elucidated.

      Methods

      In this study, we used T cell MR knockout (TMRKO) mouse to investigate the impacts of T cell MR deficiency on MI and to explore the underlying mechanisms. Echocardiography and tissue staining were used to assess cardiac function, fibrosis, and myocardial apoptosis after MI. Flow cytometry and qRT-PCR were used to detect immune cell filtration and inflammation.

      Results

      T cell MR deficiency significantly improved cardiac function, promoted myocardial repair, and inhibited myocardial apoptosis, fibrosis and inflammation after MI. Luminex assays revealed that TMRKO mice had significantly lower levels of interferon-gamma and interleukin-6 (IL-6) in serum and infarcted myocardium than littermate control mice. In cultured splenic T cells, MR deficiency suppressed IL-6 expression whereas MR overexpression enhanced IL-6 expression. ChIP assay demonstrated that MR bound to the MR response element on the promoter of IL-6 gene. Finally, T cell MR deficiency significantly suppressed accumulation of macrophages in infarcted myocardium and differentiation of pro-inflammatory macrophages, thereby alleviating the consequences of MI.

      Conclusions

      T cell MR deficiency improved pathological ventricular remodeling after MI, likely through inhibition of accumulation and differentiation of pro-inflammatory macrophages. At the molecular level, MR may work through interferon-gamma and IL-6 in T cells to exert functions in MI.

      Graphical abstract

      Key words

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