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Original Article

Korean J Physiol Pharmacol 2023; 27(4): 345-356

Published online July 1, 2023 https://doi.org/10.4196/kjpp.2023.27.4.345

Copyright © Korean J Physiol Pharmacol.

Hydrogen sulfide ameliorates abdominal aorta coarctation-induced myocardial fibrosis by inhibiting pyroptosis through regulating eukaryotic translation initiation factor 2α phosphorylation and activating PI3K/AKT1 pathway

Yaling Li1,#, Zhixiong Wu1,#, Jiangping Hu1,#, Gongli Liu1, Hongming Hu2, Fan Ouyang1,*, and Jun Yang2,*

1Department of Cardiology, Zhuzhou Central Hospital, Zhuzhou 412000, 2Department of Cardiology, The First Affiliated Hospital of University of South China, Hengyang 421001, China

Correspondence to:Jun Yang
E-mail: yangjunincn@163.com
Fan Ouyang
E-mail: 1641261977@163.com

#These authors contributed equally to this work.

Author contributions: H.H. and Y.L. performed the experiments. G.L. performed data analysis. J.H. made corrections to the manuscript. F.O. and J.Y. supervised and coordinated the study. Y.L. and Z.W. wrote the manuscript.

Received: August 18, 2022; Revised: October 31, 2022; Accepted: November 1, 2022

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

This study aimed to assess the effects of exogenous hydrogen sulfide (H2S) on abdominal aorta coarctation (AAC) induced myocardial fibrosis (MF) and autophagy in rats. Forty-four Sprague–Dawley rats were randomly divided into control group, AAC group, AAC + H2S group, and H2S control group. After a model of rats with AAC was built surgically, AAC + H2S group and H2S group were injected intraperitoneally with H2S (100 μmol/kg) daily. The rats in the control group and the AAC group were injected with the same amount of PBS. We observed that H2S can improve left ventricular function and the deposition of myocardial collagen fibers, inhibit pyroptosis, down-regulate the expression of P-eif2α in myocardial tissue, and inhibit cell autophagy by activating the phosphatidylinositol 3-kinase (PI3K)/AKT1 signaling pathway (p < 0.05). In addition, angiotensin II (1 μM) H9c2 cardiomyocytes were injured in vitro experiments, and it was also observed that pyroptosis was inhibited after H2S (400 μmol/kg) intervention, the expression of P-eif2α in cardiomyocytes was significantly down-regulated, and the PI3K/AKT1 signaling pathway was activated at the same time. Therefore, increasing the expression of P-eif2α reverses the activation of the PI3K/AKT1 signaling pathway by H2S. In conclusion, these findings suggest that exogenous H2S can ameliorate MF in rats with AAC by inhibiting pyroptosis, and the mechanism may be associated with inhibiting the phosphorylation of eif2α and activating the PI3K/AKT1 signaling pathway to inhibit excessive cell autophagy.

Keywords: Fibrosis, Hydrogen sulfide, Phosphatidylinositol 3-Kinase, Phosphorylation, Pyroptosis