MicroRNA-221 regulates endothelial nitric oxide production and inflammatory response by targeting adiponectin receptor 1

• miR-221 represses AdipoR1 expression in HUVECs.
• miR-221 inhibits adiponectin-stimulated NO production.
• miR-221 abolishes the inhibitory effect of adiponectin on NF-kB activation.

Adiponectin exerts anti-atherosclerosis property through its 2 receptors (AdipoR1 and AdipoR2). The mechanism regulating the expression of adiponectin receptors is unclear. Bioinformatics analysis showed that miR-221 targeted the 3′-untranslated region (3′UTR) of the AdipoR1 mRNA. The protein level and the mRNA level of AdipoR1 were reduced when miR-221 was expressed in human umbilical vein endothelial cells (HUVECs). Meanwhile, miR-221 repressed the activity of luciferase reporter containing the 3′UTR of AdipoR1. The inhibitory effect of miR-221 was abolished when the miR-221 binding site within the AdipoR1 3′UTR was deleted. Overexpression of miR-221 inhibited adiponectin-stimulated nitric oxide (NO) production in HUVECs. Furthermore, miR-221 abolished the inhibitory effect of adiponectin on NF-kB activation and the expression of adhesion molecules. Altogether, these results indicated that miR-221 targets AdipoR1 to regulate endothelial inflammatory response.