Proteinase‑activated receptor 2 deficiency is a protective factor against cardiomyocyte apoptosis during myocardial ischemia/reperfusion injury

Wang,Min; Ma,Yiwen; Zhang,Tiantian; Gao,Lin; Zhang,Shan; Chen,Qizhi

doi:10.3892/mmr.2019.10618

Proteinase‑activated receptor 2 deficiency is a protective factor against cardiomyocyte apoptosis during myocardial ischemia/reperfusion injury

Authors:
- Min Wang
- Yiwen Ma
- Tiantian Zhang
- Lin Gao
- Shan Zhang
- Qizhi Chen
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Affiliations: Department of Cardiology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, P.R. China, Department of Anesthesiology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, P.R. China, Department of Emergency, Tumor Hospital, Fudan University, Shanghai 200032, P.R. China
Published online on: August 26, 2019 https://doi.org/10.3892/mmr.2019.10618
Pages: 3764-3772
Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Previous studies have established that proteinase‑activated receptor 2 (PAR2) activation protects against myocardial ischemia/reperfusion injury (MI/RI). However, the role of PAR2 deficiency in MI/RI remains unclear. The aim of the present study was to examine the effect of PAR2 deficiency on cardiomyocyte apoptosis and to clarify the potential molecular mechanisms for its protective effect against MI/RI. Using a mouse model of MI/RI, cardiac function was evaluated by echocardiography, infarct size was assessed by triphenyltetrazolium chloride staining, and myocardial cell apoptosis was measured by terminal deoxynucleotide transferase‑mediated dUTP nick end‑labeling staining. Annexin V/propidium iodide staining, and expression of Bcl‑2 and cleaved PARP were determined to assess apoptosis in myocardial H9c2 cells exposed to hypoxia/reoxygenation (H/R) injury‑simulating MI/RI. Phosphorylated ERK1/2, JNK, and p38 MAPK protein expression levels were analyzed by western blotting. The findings indicated that PAR2 deficiency markedly reduced cardiomyocyte apoptosis in the MI/RI mouse model, as well as in myocardial H9c2 cells exposed to H/R. Furthermore, PAR2 knockdown clearly prevented phosphorylation of ERK1/2 and JNK in myocardial H9c2 cells. The results revealed that PAR2 deficiency alleviated MI/RI‑associated apoptosis by inhibiting phosphorylation of ERK1/2 and JNK. Therefore, targeted PAR2 silencing may be a potential therapeutic approach for alleviation of MI/RI.

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