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

  • Ebony Washington Remus
    Affiliations
    Division of Cardiology, Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA
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  • Alicia N. Lyle
    Affiliations
    Division of Cardiology, Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA
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  • Daiana Weiss
    Affiliations
    Division of Cardiology, Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA
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  • Natalia Landàzuri
    Affiliations
    Division of Cardiology, Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA
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  • Martina Weber
    Affiliations
    Division of Cardiology, Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA

    Division of Cardiology, Department of Medicine, Atlanta VA Medical Center, Georgia Institute of Technology and Emory University, Atlanta, GA, USA
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  • Charles Searles
    Affiliations
    Division of Cardiology, Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA

    Division of Cardiology, Department of Medicine, Atlanta VA Medical Center, Georgia Institute of Technology and Emory University, Atlanta, GA, USA
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  • W. Robert Taylor
    Correspondence
    Corresponding author. Division of Cardiology, Emory University School of Medicine, 101 Woodruff Circle, Suite 319 WMB, Atlanta, GA 30322, USA. Tel.: +1 404 727 8921; fax: +1 404 727 3752.
    Affiliations
    Division of Cardiology, Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA

    Division of Cardiology, Department of Medicine, Atlanta VA Medical Center, Georgia Institute of Technology and Emory University, Atlanta, GA, USA

    The Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA, USA
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      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.

      Highlights

      • Ang II increases OPN expression in a translation dependent manner in VSMCs.
      • Ang II decreases mir181a expression in VSMCs.
      • Overexpression of mir181a inhibits Ang II induced OPN expression in VSMCs.
      • OPN is essential for adhesion of VSMCs to collagen substrates.
      • Overexpression of mir181a decreases adhesion of VSMCs to collagen substrates.

      Keywords

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