Palmitic acid inhibits vascular smooth muscle cell switch to synthetic phenotype through upregulation of miR-22 expression

Abstract

Abstract Background Vascular smooth muscle cell (VSMC) phenotype switch to a dedifferentiated, synthetic phenotype has been shown to play a vital role in many 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. Here, we aimed to examine the effects of palmitic acid (PA), the most common saturated fatty acid in circulation, on VSMC phenotype and the underlying mechanism. Methods The effect of the PA on VSMC was measured by live/dead and EdU assays, as well as flow cytometry. Migration ability of VSMCs was determined by transwell assay. The underlying targets of miR-22 was predicted using bioinformatics online tools, and comfirmed by luciferase reporter assay. The RNA and protein expression of certain gene or protein was detected by qRT-PCR and western blot, respectively. Results We found that 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 effects of PA on VSMC phenotype modulation, suggesting that PA modulated VSMC phenotype through upregulation of miR-22 expression. In addition, 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 inhibitive effect of EVI1 on synthetic phenotype switch of VSMCs. Conclusions 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.