Abstract
Oxidative stress is a crucial factor and key promoter of a variety of cardiovascular diseases associated with cardiomyocyte injury. Emerging literatures suggest that pyroptosis plays a key role in cardiac damages. However, whether pyroptosis contributes to cardiomyocyte injury under oxidative stress and the underlying molecular mechanisms are totally unclear. This study was designed to investigate the potential role of pyroptosis in H(2)O(2)-induced cardiomyocyte injury and to elucidate the potential mechanisms. Primary cardiomyocytes from neonatal Wistar rats were utilized. These myocytes were treated with different concentrations of H(2)O(2) (25, 50, and 100 μM) for 24 h to induce oxidative injury. Our results indicated that mRNA and protein levels of ASC were remarkably upregulated and caspase-1 was activated. Moreover, the expressions of inflammatory factors IL-1β and IL-18 were also increased. Luciferase assay showed that miR-599 inhibited ASC expression through complementary binding with its 3'UTR. MiR-599 expression was substantially reduced in H(2)O(2)-treated cardiomyocytes. Upregulation of miR-599 inhibited cardiomyocyte pyroptosis under oxidative stress, and opposite results were found by decreasing the expression of miR-599. Consistently, miR-599 overexpression ameliorated cardiomyocyte injury caused by H(2)O(2). Therefore, miR-599 could be a promising therapeutic approach for the management of cardiac injury under oxidative condition.