Overexpression of mir181a protects against Ang II induced osteopontin expression in VSMC

Abstract

Angiotensin II (Ang II) promotes reactive oxygen species production, migration and ultimately hypertrophy in vascular smooth muscle cells (VSMCs). MicroRNAs (miRNAs) are critical regulators of protein expression in cardiovascular disease. However, the relationship between Ang II and miRNAs in VSMCs has yet to be determined. Osteopontin (OPN) is a multifunctional protein found in abundance in atherosclerotic plaques and in the injured arterial wall. In a mouse model of hypertension, we found that aortic OPN protein expression was increased 2‐fold after 7 days of 0.75mg/kg/day Ang II treatment in C57Bl/6 mice (p < 0.001). In vitro, we found Ang II increased OPN protein expression 4hrs after treatment by 420%±54 (p < 0.03) in cultured VSMCs. Literature searches revealed OPN mRNA as a potential target of mir181a. We found that Ang II decreased mir181a expression by 52%±7 (p < 0.0001) 24hrs post stimulation in VSMCs. We observed that over expression of mir181a inhibited Ang II induced increases in OPN protein expression at 4hrs in VSMCs by 69%±9 (p < 0.05). We conclude that Ang II decreases mir181a expression while increasing OPN protein expression, and that over expressing mir181a blocks Ang II induced OPN protein translation. These results suggest that mir181a may be a novel therapeutic approach to alter OPN protein expression during Ang II induced vascular dysfunction.