Overexpression of miR-223 inhibits foam cell formation by inducing autophagy in vascular smooth muscle cells.

backgroundVascular smooth muscle cells (VSMCs) play an important role in foam cell formation, a hallmark of atherosclerosis obliterans (ASO). We recently demonstrated that miR-223 is significantly upregulated both in atherosclerotic arteries and in the serum sample of ASO patients. However, it is still unknown if miR-223 is implicated in the foam cell formation of VSMCs. The current study aimed to investigate the role of miR-223 in the foam cell formation of VSMCs.

methodsArtery and serum samples were collected from ASO patients. Human VSMCs were isolated from the normal arteries of healthy donors. For miR-223 overexpression, miR-223 mimic was transfected into VSMCs using Lipofectamine 2000. Foam cell formation was evaluated by lipid accumulation using Oil Red O staining. Luciferase assay was adopted to confirm the target gene of miRNA.

resultsmiR-223 was significantly upregulated in both the arteries and serum samples from ASO patients. miR-223 overexpression significantly inhibited the foam cell formation and decreased total intracellular cholesterol levels in VSMCs. miR-223 overexpression induced autophagy of VSMCs. Blocking autophagy by 3-methyladenine or autophagy-related 7 (Atg7) siRNAs attenuated the inhibitory effect of miR-223 overexpression on foam cell formation. Luciferase assay showed that IGF-1R is a direct target of miR-223. miR-223 overexpression reduced protein levels of IGF-1R expression and the phosphorylated form of PI3K and Akt proteins.

conclusionsmiR-223 overexpression inhibited foam cell formation in VSMCs, at least partially, via inducing autophagy. The IGF-1R/PI3K/Akt signaling pathway may be also involved in this mechanism.