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

Abstract

The 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.

The Efficacy and Safety of Bisoprolol in the Treatment of Myocardial Infarction with Cardiac Insufficiency

“…Bisoprolol is more selective for β 1 receptors than metoprolol and attilol. In addition, reliable efficacy has been achieved in the treatment of congestive heart failure [ 13 , 14 ]. However, the effect of bisoprolol on myocardial infarction and cardiac insufficiency is unclear.…”

Protective effects of safranal on hypoxia/reoxygenation‑induced injury in H9c2 cardiac myoblasts via the PI3K/AKT/GSK3β signaling pathway

“…The intracellular PI3K/AKT/GSK3β signal transduction pathway serves important biological roles in cellular mechanisms, such as apoptosis, cell survival and proliferation (66). During MIRI, the RISK signaling pathway is activated and the expression levels of numerous types of proteins with endogenous protective effects increase (14).…”

Verapamil downregulates iron uptake and upregulates divalent metal transporter 1 expression in H9C2 cardiomyocytes

“…The H9C2 cardiomyocytes (American Type Culture Collection, USA), a permanent cell line derived from the embryonic rat ventricle, were grown in Dulbecco's modified Eagle's medium (Glutamax; Life Technologies), supplemented with 10% (v/v) heat‐inactivated fetal bovine serum, 100 U/ml of sodium penicillin G and 100 μg/ml of streptomycin sulfate [18]. The cell number was determined by trypan blue exclusion under the microscope, and the required number of cells was placed into flasks (for maintenance) or in six‐well plates and 35‐mm culture dishes.…”