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

• Type of Material: Article
• Authors: Ebony Washington Remus, Emory University; Alicia N. Lyle, Emory University; Daiana Weiss, Emory University; Natalia Landazuri, Emory University; Martina Weber, Emory University; Charles D Searles Jr., Emory University; W Robert Taylor, Emory University
• Language: English
• Date: 2013-05
• Publisher: Elsevier: 12 months
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2013 Elsevier Ireland Ltd. All rights reserved.
• License: Creative Commons Attribution-NonCommerical-NoDerivs 3.0 Unported
• Final Published Version (URL): http://dx.doi.org/10.1016/j.atherosclerosis.2013.01.037
• Title of Journal or Parent Work: Atherosclerosis
• ISSN: 0021-9150
• Volume: 228
• Issue: 1
• Start Page: 168
• End Page: 174
• Grant/Funding Information: This work was supported by NIH grants NIH RO1 HL090584, NIH RO1HL062820 and NIH (F32) 1F31HL092772-01 (EWR).
• Keywords: Translational control; Angiotensin II; Osteopontin; MicroRNA
• Research Categories: Health Sciences, General

Abstract

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.