Bisoprolol, a β1 antagonist, protects myocardial cells from ischemia–reperfusion injury via PI3K/AKT/GSK3β pathway

• DOI: 10.1111/fcp.12562
• Publication Date: 2020-05-04T05:42:53Z
• Authors: Jing Wang; Jing Liu; Liang Xie; Xiaomin Cai; Xiaohua Ma; Jianbin Gong
• Keywords: Male; Cardiotonic Agents; Glycogen Synthase Kinase 3 beta; Myocardial Reperfusion Injury; Adrenergic beta-1 Receptor Antagonists; Rats; 3. Good health; Rats, Sprague-Dawley; Disease Models, Animal; Phosphatidylinositol 3-Kinases; 03 medical and health sciences; 0302 clinical medicine; Animals; Bisoprolol; Myocytes, Cardiac; Proto-Oncogene Proteins c-akt; Signal Transduction

AbstractThe aim of this work was to explore whether bisoprolol plays a protective role in cardiomyocytes against ischemia–reperfusion injury via PI3K/AKT/ GSK3β pathway. We pretreated male Sprague Dawley (SD) rats with bisoprolol by oral administration prior to 0.5 h ischemia/4 h reperfusion. Myocardial infarct size and serum levels of cTnI and CK‐MB were measured. In vitro, H9c2 cells were treated with hypoxia and reoxygenation, followed by measurement of cell viability, apoptosis, ROS production, cytometry, activities of AKT, GSK3β, and p‐38 in the presence and absence of GSK3β siRNA. We found that bisoprolol reduced infarct size from 44% in I/R group to 31% in treated group (P < 0.05). The levels of cTnI and CK‐MB were decreased from 286 ± 7 pg/mL and 32.2 ± 2 ng/mL in I/R group to 196 ± 2 pg/mL and 19.6 ± 0.9 ng/mL in the treated group, respectively (P < 0.05). Bisoprolol also increased cell viability while decreased apoptosis and ROS production in the treatment of hypoxia/ reoxygenation. Furthermore, bisoprolol increased AKT and GSK3β phosphorylation, an effect that was immediately eliminated by LY294002. GSK3β‐specific siRNA experiment further confirmed that bisoprolol protected the myocardium against hypoxia/reoxygenation‐induced injury via suppressing GSK3β activity. In conclusion, bisoprolol protected myocardium against ischemia–reperfusion injury via the PI3K/AKT/ GSK3β pathway.