Abstract
Synthetic phenotype switch of vascular smooth muscle cells (VSMCs) has been shown to play key roles in vascular diseases. Mounting evidence has shown that fatty acid metabolism is highly associated with vascular diseases. However, how fatty acids regulate VSMC phenotype is poorly understood. Hence, the effects of palmitic acid (PA) on VSMC phenotype were determined in this study. The effect of the PA on VSMCs was measured by live/dead and EdU assays, as well as flow cytometry. Migration ability of VSMCs was evaluated using transwell assay. The underlying targets of miR-22 were predicted using bioinformatics online tools, and confirmed by luciferase reporter assay. The RNA and protein expression of certain gene was detected by qRT-PCR or western blot. PA inhibited VSMC switch to synthetic phenotype, as manifested by inhibiting VSMC proliferation, migration, and synthesis. PA upregulated miR-22 in VSMCs, and miR-22 mimics exerted similar effects as PA treatment, inhibiting VSMC switch to synthetic phenotype. Inhibition of miR-22 using miR-22 inhibitor blocked the impacts of PA on VSMC phenotype modulation, suggesting that PA modulated VSMC phenotype through upregulation of miR-22 expression. We found that ecotropic virus integration site 1 protein homolog (EVI1) was the target of miR-22 in regulation of VSMC phenotype. Overexpression of miR-22 or/and PA treatment attenuated the inhibition of EVI1 on switch of VSMCs. These findings suggested that PA inhibits VSMC switch to synthetic phenotype through upregulation of miR-22 thereby inhibiting EVI1, and correcting the dysregulation of miR-22/EVI1 or PA metabolism is a potential treatment to vascular diseases.