1. Academic Validation
  2. Inhibition of cathepsin S attenuates myocardial ischemia/reperfusion injury by suppressing inflammation and apoptosis

Inhibition of cathepsin S attenuates myocardial ischemia/reperfusion injury by suppressing inflammation and apoptosis

  • J Cell Physiol. 2021 Feb;236(2):1309-1320. doi: 10.1002/jcp.29938.
Ke Peng 1 Hong Liu 2 Bin Yan 3 4 Xiao-Wen Meng 1 Shao-Yong Song 1 Fu-Hai Ji 1 Zhengyuan Xia 2 5
Affiliations

Affiliations

  • 1 Department of Anesthesiology, First Affiliated Hospital of Soochow University, Suzhou, China.
  • 2 Department of Anesthesiology and Pain Medicine, University of California Davis Health, Sacramento, California.
  • 3 Department of Intervention and Cell Therapy, Peking University Shenzhen Hospital, Shenzhen, China.
  • 4 Department of Computer Science, The University of Hong Kong, Pokfulam, Hong Kong.
  • 5 Department of Anesthesiology, The University of Hong Kong, Pokfulam, Hong Kong.
Abstract

Myocardial ischemia/reperfusion (I/R) injury leads to high mortality and morbidity due to the incomplete understanding of the underlying mechanism and the consequent lack of effective therapy. The present study revealed and validated key candidate genes in relation to inflammation and Apoptosis pathways underlying myocardial I/R injury. Cathepsin S was identified as the top hub protein based on the protein-protein interaction analysis, and, thus, its role during myocardial I/R injury was further investigated. Myocardial I/R in mice resulted in significantly increased levels of myocardial injury biomarkers (cardiac troponin I, lactic dehydrogenase, and creatinine kinase-MB) and inflammatory cytokines (interleukin-1β [IL-1β], IL-6, and tumor necrosis factor-α), elevated Apoptosis rate, and upregulated protein expression of cleaved Caspase-8, cleaved Caspase-3, and cleaved poly ADP-ribose polymerase. These abovementioned changes were blocked by two different selective Cathepsin S inhibitors, LY3000328 or MIV-247. Moreover, Kaplan-Meier survival plot showed that Cathepsin S inhibition improved 21-day survival rate following myocardial I/R injury. This study demonstrated that the inhibition of Cathepsin S alleviated myocardial I/R-induced injury by suppressing inflammation and Apoptosis, which may be used in clinical applications of cardioprotection.

Keywords

apoptosis; cardioprotection; cathepsin S; inflammation; myocardial ischemia/reperfusion injury.

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