The Korean Journal of Physiology and Pharmacology

The Korean Society of Pharmacology (대한약리학회)
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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 Li (Department of Cardiology, Zhuzhou Central Hospital) ;
  • Zhixiong Wu (Department of Cardiology, Zhuzhou Central Hospital) ;
  • Jiangping Hu (Department of Cardiology, Zhuzhou Central Hospital) ;
  • Gongli Liu (Department of Cardiology, Zhuzhou Central Hospital) ;
  • Hongming Hu (Department of Cardiology, The First Affiliated Hospital of University of South China) ;
  • Fan Ouyang (Department of Cardiology, Zhuzhou Central Hospital) ;
  • Jun Yang (Department of Cardiology, The First Affiliated Hospital of University of South China)
  • Received : 2022.08.18
  • Accepted : 2022.11.01
  • Published : 2023.07.01
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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

Acknowledgement

This study was supported by grant from the National Natural Science Foundation of China (Grant Nos. 81870230), Hunan Natural Science Foundation (2022JJ40885).

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