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

Background: Vascular 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. Methods: This study used a hypoxicinduced 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. Results: The 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. Conclusions: Results 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.