TNFα-induced downregulation of microRNA-186 contributes to apoptosis in rat primary cardiomyocytes.

Progressive loss of cardiac cardiomyocytes is involved in pathogenesis of heart failure. Inflammation is considered as a major risk factor that triggers cardiomyocytes apoptosis or induces cellular damage. Proinflammatory cytokines such as TNFα can directly activate cell apoptosis or promote oxidant production that damages cellular structure eventually. We investigated TNFα mediated apoptosis in cultured rat primary cardiomyocytes. Annexin V/PI staining and apoptosis biomarker expression were used to examine cardiomyocytes cell apoptosis response. We also identified key microRNA that plays a regulatory role in this pathway with genetic and biochemical approaches. Apoptosis Inducing Factor (AIF) expression was found to be upregulated with 10μg/ml or 50μg/ml TNFα stimulation for 24h, which was associated with apoptotic index. Subsequently, miR-186 was identified as direct regulator of AIF in TNFα mediated cardiomyocytes apoptosis from microRNA expression profiling. miR-186 level was downregulated with TNFα treatment that was correlated with AIF induction. Last, in the rescue experiment, miR-186 mimic protected cardiomyocytes against TNFα mediated apoptosis. Collectively, the results suggest TNFα-induced AIF upregulation contributes to apoptosis in rat primary cardiomyocytes through regulating miR-186 expression, which implies miR-186 could be a potential therapeutic target for preventing inflammation associated cardiac damage.