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The mechanism of mitochondrial damage of atrial myocytes mediated by GSDMD-N promoting atrial remodeling in diabetes
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  • Hai-Feng Zhang,
  • Meng-Zhu Zhou,
  • Yue Zhang,
  • meng yuan,
  • Lijun Cheng,
  • Xing Liu,
  • Tong Liu,
  • Changle Liu
Hai-Feng Zhang
Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease
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Meng-Zhu Zhou
Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease
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Yue Zhang
Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease
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meng yuan
Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease
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Lijun Cheng
Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease
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Xing Liu
Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease
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Tong Liu
Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease
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Changle Liu
Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease

Corresponding Author:lcl1979_2001@163.com

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Abstract

Gasdermin D (GSDMD) can induce pyroptosis and mitochondrial damage, thereby promoting the occurrence and development of diabetes (DM) related atrial fibrillation (AF). We aimed to investigate the mechanism of mitochondrial damage in atrial myocytes mediated by GSDMD N-terminal domain (GSDMD-N) in DM related AF. We established a rat DM model and demonstrated that under high blood glucose stimulation, the NLRP3 inflammasome pathway can activate GSDMD into active GSDMD-N, thereby exacerbating mitochondrial damage and pyroptosis of atrial myocytes in DM rats, leading to atrial remodeling. Meanwhile, DM can act on fibroblasts, promote collagen synthesis and inhibit its breakdown, and lead to myocardial fibrosis. In addition, inflammation and oxidative stress mediated by DM can promote atrial electrical remodeling, while changes in myocardial cell ultrastructure caused by myocardial fibrosis and pyroptosis can also exacerbate electrical remodeling. The interaction between structural reconstruction and electrical reconstruction jointly promotes the occurrence and development of AF.