miR181a protects against angiotensin II-induced osteopontin expression in vascular smooth muscle cells

Objective: Osteopontin (OPN) is a multifunctional protein found in abundance in atherosclerotic plaques. Angiotensin II (Ang II) promotes atherosclerosis by inducing adhesion and migration of vascular smooth muscle cells (VSMCs). MicroRNAs (miRNAs) are critical regulators of protein expression. However, the relationship between Ang II, miRNAs and OPN has yet to be fully explored. Methods and results: Using cultured VSMCs, we found that Ang II increased cellular OPN protein expression 4 h after treatment by 420 +/- 54% (p < 0.03) in a translation dependent manner. Sequence analysis revealed a putative binding site for mir181a and raised the possibility that miR181a is a potential regulatory mechanism for OPN expression. We demonstrated that Ang II decreased miR181a expression by 52 +/- 7% (p < 0.0001) and overexpressing miR181a inhibited Ang II induced increases in OPN protein expression by 69 +/- 9% (p < 0.05). Furthermore, we demonstrated that miR181a is functionally important in that overexpression of miR181a inhibited VSMCs adhesion to collagen in response to Ang II as compared to controls by 36 +/- 4%. (p < 0.05) Conclusions: These results demonstrate that miR181a regulates OPN expression and that altering miR181a expression may be a novel therapeutic approach to modulate OPN protein expression. (C) 2013 Elsevier Ireland Ltd. All rights reserved.