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Original Article

Korean J Physiol Pharmacol 2024; 28(2): 129-143

Published online March 1, 2024

Copyright © Korean J Physiol Pharmacol.

Effects of gas signaling molecule SO2 in cardiac functions of hyperthyroid rats

Qi Yang1,#, Ting Yang2,#, Xing Liu1, Shengquan Liu1, Wei Liu1, Liangui Nie1,*, Chun Chu3,*, and Jun Yang1,*

1Department of Cardiology, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang 421000, 2School of Pharmaceutical Science of University of South China, Hengyang 421000, 3Department of Pharmacy, The Second Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang 421000, Hunan, China

Correspondence to:Jun Yang
Chun Chu
Liangui Nie

#These authors contributed equally and share first authorship.

Author contributions: Q.Y. was responsible for execution of the experiments and the writing of the manuscript. T.Y. and X.L. were participated in molecular biology testing and experimental design. S.L. and W.L. were responsible for the execution of experiments and data analysis. L.N., C.C., and J.Y. were responsible for the design of the experiment. All authors contributed to this work and approved the submitted version.

Received: November 7, 2023; Revised: November 30, 2023; Accepted: December 11, 2023


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: Apoptosis, Endoplasmic reticulum stress, Hippo signaling pathway, Hyperthyroidism-induced cardiomyopathy, Sulfur dioxide