Up-regulation of PERK/Nrf2/HO-1 axis protects myocardial tissues of mice from damage triggered by ischemia-reperfusion through ameliorating endoplasmic reticulum stress

Cardiovascular Diagnosis and Therapy
Jichun WangHong Jiang

Abstract

Ischemia-reperfusion (I/R) injury, which leads to additionally cardiac tissue damage, is a severe adverse effect of reperfusion therapeutics used for the treatment of acute myocardial infarction. Agents capable of alleviating I/R-induced myocardial injury are urgently needed. In this study, we investigated whether up-regulation of PERK/Nrf2/HO-1 axis provided protective roles for murine myocardium suffering I/R intervention. The in vivo I/R model was formed by ligation of the left anterior descending (LAD) coronary artery of C57BL/6J mice. All animals were assigned into the following groups at random: sham, I/R, rAAV9-PERK + I/R, rAAV9-Nrf2 + I/R, rAAV9-HO-1 + I/R, siRNA-HO-1 + rAAV9-PERK + I/R. The ligation of LAD was released after 30 min of ischemia, which was followed by reperfusion of LAD for 4 h. Then the cardiac tissues and blood serum were collected. TUNEL staining, ELISA assay, TTC staining, Western blotting and real-time PCR were used to determine I/R injury-related indicators. Our results showed that I/R administration triggered cardiomyocytes apoptosis and LDH and CK-MB release, yet overexpression of PERK decreased cellular apoptosis index in the cardiac tissue and reduced levels of LDH and CK-MB in the serum. We fu...Continue Reading

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