MiR-210 inhibits hypoxia-induced apoptosis of smooth muscle cells via targeting MEF2C.

backgroundVascular smooth muscle cell (VSMC) apoptosis plays an important role in vascular remodeling and atherosclerotic plaque instability. Growing evidence suggests that microRNAs (miRNAs) play a critical role in VSMC function, however, the underlying mechanism remains unclear.

methodsThis study used a hypoxic-induced VSMC apoptosis model. Expression of miR-210, its target MEF2C, and other key factors of apoptosis were detected and measured by real-time PCR and western blot. Luciferase reporter assay was performed to detect the miR-210 target. The function of miR-210 in apoptosis was determined using flow cytometric cell apoptosis assays. The relationship between miR-210 and MEF2C was confirmed and key apoptosis factors were detected.

resultsThe restoration of miR-210 function in cells transfected with a miR-210 mimic inhibited VSMC apoptosis compared to control. MiR-210 overexpression inhibited the expression of Bax, Bad, cleaved Caspase-3, and promoted the expression of Bcl-2, Caspase-3, Caspase-9 and mitochondrial cytochrome c at both the mRNA and protein levels. Results also found that MEF2C was a direct target of miR-210 in hypoxic VSMCs. Further, miR-210 suppressed MEF2C expression by directly binding to its 3'-untranslated region and the expression of miR-210 was negatively correlated with MEF2C mRNA levels.

conclusionsResults from this study provide the first evidence that miR-210 can inhibit apoptosis by targeting MEF2C in hypoxic VSMCs and may support the development of new biomarkers and therapeutic targets for atherosclerosis.