2. Academic Validation
  3. Irisin improves diabetic cardiomyopathy-induced cardiac remodeling by regulating GSDMD-mediated pyroptosis through MITOL/STING signaling

Irisin improves diabetic cardiomyopathy-induced cardiac remodeling by regulating GSDMD-mediated pyroptosis through MITOL/STING signaling

  • Biomed Pharmacother. 2024 Jan 2:171:116007. doi: 10.1016/j.biopha.2023.116007.
Linhe Lu 1,  Yalan Shao 2,  Xiang Xiong 3,  Jipeng Ma 2,  Mengen Zhai 2,  Guofang Lu 4,  Liqing Jiang 2,  Ping Jin 2,  Jiayou Tang 2,  Jian Yang 2,  Yang Liu 5,  Weixun Duan 6,  Jincheng Liu 7
Affiliations

Affiliations

  • 1 Department of Cardiovascular Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China; Department of Physiology and Pathophysiology, National Key Discipline of Cell Biology, Fourth Military Medical University, Xi'an 710032, China.
  • 2 Department of Cardiovascular Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China.
  • 3 Department of Cardiovascular Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China; Department of Cardiothoracic Surgery, The Affiliated Hospital of Jiujiang University, Jiujiang, Jiangxi 332000, China.
  • 4 Department of Physiology and Pathophysiology, National Key Discipline of Cell Biology, Fourth Military Medical University, Xi'an 710032, China; State Key Laboratory of Cancer Biology and National Clinical Research Center for Digestive Diseases, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an 710032, China.
  • 5 Department of Cardiovascular Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China. Electronic address: liuyangxijing@126.com.
  • 6 Department of Cardiovascular Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China. Electronic address: duanweixun@126.com.
  • 7 Department of Cardiovascular Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China. Electronic address: Liujch69@sina.com.
PMID: 38171238 DOI: 10.1016/j.biopha.2023.116007
Abstract

Diabetic cardiomyopathy (DCM) is a common complication of diabetes mellitus (DM). However, the mechanisms underlying DCM-induced cardiac injury remain unclear. Recently, the role of Cyclic GMP-AMP Synthase/stimulator of interferon gene (cGAS/STING) signaling and Pyroptosis in DCM has been investigated. Based on our previous results, this study was designed to examine the impact of irisin, mitochondrial ubiquitin ligase (MITOL/MARCH5), and cGAS/STING signaling in DCM-induced cardiac dysfunction and the effect of gasdermin D (GSDMD)-dependent Pyroptosis. High-fat diet-induced mice and H9c2 cells were used for cardiac geometry and function or pyroptosis-related biomarker assessment at the end of the experiments. Here, we show that DCM impairs cardiac function by increasing cardiac fibrosis and GSDMD-dependent Pyroptosis, including the activation of MITOL and cGAS/STING signaling. Our results confirmed that the protective role of irisin and MITOL was partially offset by the activation of cGAS/STING signaling. We also demonstrated that GSDMD-dependent Pyroptosis plays a pivotal role in the pathological process of DCM pathogenesis. Our results indicate that irisin treatment protects against DCM injury, mitochondrial homeostasis, and Pyroptosis through MITOL upregulation.

Keywords

Diabetic cardiomyopathy; Gasdermin D; Irisin; Mitochondrial ubiquitin ligase; Pyroptosis; Stimulator of interferon gene.

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