Myocardial ischemia-reperfusion injury (MI/RI), a complication of myocardial injury, is associated with high rates of mortality and disability. We aimed to explore the effect of nicorandil™ against MI/RI and investigated the underlying molecular mechanisms. In this in vitro study, hypoxia/reoxygenation (H/R) processing of H9c2 cells significantly suppressed the expressions of IL33 and ST2, reduced cell viability, increased production of reactive oxygen species, downregulated protein expression of Bcl-2, upregulated protein expressions of Bax, cleaved caspase3, and cleaved PARP, increased intracellular calcium overload, and induced cell apoptosis. Nicorandil processing reduced H/R-induced H9c2 cell damage. Nicorandil processing ameliorated the H/R-induced inhibition of the IL33 and ST2 expression in H9c2 cells. 5-Hydroxydecanoate blocked the effects of nicorandil on H9c2 cell viability, ROS production, and apoptosis and inhibited both IL33 and ST2. Similarly, the protective effect of nicorandil was restrained after inhibition of the IL33/ST2 pathway. Our findings suggest that the protective effect of nicorandil against H/R-induced H9c2 cell apoptosis was mediated through IL33/ST2 signaling pathway.
Keywords: 5-Hydroxydecanoate; Apoptosis; IL33/ST2 signal; Ischemia/reperfusion; Nicorandil.
© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.