Cardioprotective effects of soluble guanylate cyclase and its α1 subunit on myocardial ischemia/reperfusion injury through the regulation of the PGC-1α/UCP2 pathway

Abstract

Abstract Purpose The present study aimed to investigate the cardioprotective potential of soluble guanylate cyclase (sGC) and its 1 subunit on myocardial ischemia/reperfusion injury (MIRI), as well as the potential mechanism. Methods SD rats were subjected to left coronary artery ischemia/reperfusion, and H9C2 cells were cultured in an Anaero Pack anaerobic bag to induce a MIRI model. Myocardial infarction area, myocardial tissue morphology and myocardial tissue ultrastructure were observed by TTC, HE and transmission electron microscopy, respectively. Myocardial tissues of each group were examined by colorimetric assay for CAT, GSH-Px and SOD, TUNEL staining for apoptosis, ELISA for cGMP, and Western blot for protein expression of Capase3, sGCα1, PGC-1α and UCP2. Results In vivo, sGC exerted cardioprotective effects, as shown by a reduced myocardial infarct size. sGC also reduced oxidative stress and apoptosis in myocardial cells, which was associated with the activation of PGC-1α and UCP2. The protein expression of sGCα1 changes with the activity of sGC. In vitro, sGCα1 inhibited oxidative stress and apoptosis in H9C2 cells by activating the PGC-1α/UCP2 pathway. Conclusion Our results suggest that sGC and its α1 subunit exert cardioprotective effects by inhibiting oxidative stress and cell apoptosis during MIRI and reveal a potential mechanism involving the PGC-1α/UCP2 pathway.