The Korean Journal of Physiology and Pharmacology

The Korean Society of Pharmacology (대한약리학회)
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Effects of gas signaling molecule SO2 in cardiac functions of hyperthyroid rats

  • Qi Yang (Department of Cardiology, The First Affiliated Hospital, Hengyang Medical School, University of South China) ;
  • Ting Yang (School of Pharmaceutical Science of University of South China) ;
  • Xing Liu (Department of Cardiology, The First Affiliated Hospital, Hengyang Medical School, University of South China) ;
  • Shengquan Liu (Department of Cardiology, The First Affiliated Hospital, Hengyang Medical School, University of South China) ;
  • Wei Liu (Department of Cardiology, The First Affiliated Hospital, Hengyang Medical School, University of South China) ;
  • Liangui Nie (Department of Cardiology, The First Affiliated Hospital, Hengyang Medical School, University of South China) ;
  • Chun Chu (Department of Pharmacy, The Second Affiliated Hospital, Hengyang Medical School, University of South China) ;
  • Jun Yang (Department of Cardiology, The First Affiliated Hospital, Hengyang Medical School, University of South China)
  • Received : 2023.11.07
  • Accepted : 2023.12.11
  • Published : 2024.03.01
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Abstract

Sulfur dioxide (SO2), a novel endogenous gas signaling molecule, is involved in the regulation of cardiac function. Exerting a key role in progression of hyperthyroidism-induced cardiomyopathy (HTC), myocardial fibrosis is mainly caused by myocardial apoptosis, leading to poor treatment outcomes and prognoses. This study aimed to investigate the effect of SO2 on the hyperthyroidism-induced myocardial fibrosis and the underlying regulatory mechanisms. Elisa, Masson staining, Western-Blot, transmission electron microscope, and immunofluorescence were employed to evaluate the myocardial interstitial collagen deposition, endoplasmic reticulum stress (ERS), apoptosis, changes in endogenous SO2, and Hippo pathways from in vitro and in vivo experiments. The study results indicated that the hyperthyroidism-induced myocardial fibrosis was accompanied by decreased cardiac function, and down-regulated ERS, apoptosis, and endogenous SO2-producing enzyme aspartate aminotransferase (AAT)1/2 in cardiac myocytes. In contrast, exogenous SO2 donors improved cardiac function, reduced myocardial interstitial collagen deposition, up-regulated AAT1/2, antagonized ERS and apoptosis, and inhibited excessive activation of Hippo pathway in hyperthyroid rats. In conclusion, the results herein suggested that SO2 inhibited the overactivation of the Hippo pathway, antagonized ERS and apoptosis, and alleviated myocardial fibrosis in hyperthyroid rats. Therefore, this study was expected to identify intervention targets and new strategies for prevention and treatment of HTC.

Keywords

Acknowledgement

This project was supported by the National Natural Science Foundation of China (No. 81870230 and No. 82074236), Clinical Major Projects of Hunan Provincial Health Commission (No. 20201913), the Natural Science Foundation of Hunan Province (No. 2021JJ70035, No. 2021JJ40499 and No. 2021JJ70116), the Hunan Provincial Graduate Student Research and Innovation Program (No. CX20231002).

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