Interaction Between COX-2 and ER Stress is Involved in the Apoptosis-induced Myocardial Ischemia/reperfusion Injury

Overview

Journal Am J Transl Res

Specialty General Medicine

Date 2022 Jun 15

PMID 35702111

Authors

Wenhui Tao

Lingui Li

Junkai Hu

Shangxian Xu

Biying Wang

Jun Ding

Mian Zhang

Xiaowen Meng

Xiang Wei

Xisheng Shan

Ke Peng

HuaYue Liu

Fuhai Ji

Affiliations

Soon will be listed here.

Abstract

Purpose: Apoptosis induced by excessive endoplasmic reticulum (ER) stress is accompanied by the occurrence and progression of myocardial ischemia/reperfusion (I/R) injury. COX-2 is also known to affect the development of I/R damage in myocardium. However, the interaction between COX-2 and ER stress in aggravating myocardial I/R lesion is not well characterized. Therefore, the purpose of our research was to explore the interaction between COX-2 and ER stress on myocardial apoptosis.

Methods: The left anterior descending (LAD) coronary artery was ligatured with a 6-0# suture for 0.5 hours and subsequently subjected to reperfusion for 3 hours to simulate myocardial I/R in mice. Oxygen glucose deprivation/reoxygenation (OGD/R) was performed on H9c2 cells to construct an in vitro model of this experiment. NS398 (COX-2 specific inhibitor) and Salubrinal (Sal, ER stress inhibitor) were administered to assess the function of COX-2 and ER stress in myocardial I/R impairment. CCK-8 assay was used to evaluate the viability of H9c2 cells under different treatment conditions. TUNEL and Hoechst staining were used to detect the occurrence of apoptosis. Infarct area/area at risk and Hematoxylin-eosin stained sections were assessed after I/R. Protein expressions of glucose-regulated protein 78 (GRP78), COX-2, phosphorylation of eukaryotic translation initiation factor 2 alpha (p-eIF2α), CCAAT/enhancer-binding protein homologous protein (CHOP), and Cleaved caspase 3 in the myocardium were examined using Western blotting. Changes in Cleaved caspase 3 expression in myocardial slices were measured by immunohistochemistry.

Results: Sal or NS398 partly reduced I/R-induced damage as testified by the apparent decrease in infarct size after I/R and reduced cell viability following OGD/R. Sal distinctly increased p-eIF2α, but caused decreased expression of COX-2, Cleaved caspase 3, and ER stress-associated proteins after I/R, suggesting that Sal effectively inhibited ER stress, apoptosis, and COX-2. Pretreatment with NS398 blocked I/R or OGD/R-induced upregulation of COX-2, Cleaved caspase 3, and ER stress-related marker proteins.

Conclusions: Interaction of COX-2 and ER stress regulates apoptosis and contributes to Myocardial lesion induced by I/R.

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