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

Vascular 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.

miR-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.

Artery 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.

miR-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. Conclusions: miR-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.