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A repressor protein, Mnt, is a novel negative regulator of vascular smooth muscle cell hypertrophy by angiotensin II and neointimal hyperplasia by arterial injury

  • Takehiko Takayanagi
    Affiliations
    Cardiovascular Research Center, Temple University School of Medicine, 3500 N. Broad Street, Philadelphia, PA 19140, USA

    Department of Physiology, Temple University School of Medicine, 3500 N. Broad Street, Philadelphia, PA 19140, USA
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  • Akito Eguchi
    Affiliations
    Cardiovascular Research Center, Temple University School of Medicine, 3500 N. Broad Street, Philadelphia, PA 19140, USA

    Department of Physiology, Temple University School of Medicine, 3500 N. Broad Street, Philadelphia, PA 19140, USA
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  • Akira Takaguri
    Affiliations
    Cardiovascular Research Center, Temple University School of Medicine, 3500 N. Broad Street, Philadelphia, PA 19140, USA

    Department of Physiology, Temple University School of Medicine, 3500 N. Broad Street, Philadelphia, PA 19140, USA
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  • Akinari Hinoki
    Affiliations
    Cardiovascular Research Center, Temple University School of Medicine, 3500 N. Broad Street, Philadelphia, PA 19140, USA

    Department of Physiology, Temple University School of Medicine, 3500 N. Broad Street, Philadelphia, PA 19140, USA
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  • Allison M. Bourne
    Affiliations
    Cardiovascular Research Center, Temple University School of Medicine, 3500 N. Broad Street, Philadelphia, PA 19140, USA

    Department of Physiology, Temple University School of Medicine, 3500 N. Broad Street, Philadelphia, PA 19140, USA
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  • Katherine J. Elliott
    Affiliations
    Cardiovascular Research Center, Temple University School of Medicine, 3500 N. Broad Street, Philadelphia, PA 19140, USA

    Department of Physiology, Temple University School of Medicine, 3500 N. Broad Street, Philadelphia, PA 19140, USA
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  • Peter J. Hurlin
    Affiliations
    Department of Cell and Developmental Biology, Oregon Health and Science University, Portland, OR, USA
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  • Satoru Eguchi
    Correspondence
    Corresponding author. Cardiovascular Research Center, Temple University School of Medicine, Room 1051 MERB, 3500 N. Broad Street, Philadelphia, PA 19140, USA. Tel.: +1 215 707 0169; fax: +1 215 707 8378.
    Affiliations
    Cardiovascular Research Center, Temple University School of Medicine, 3500 N. Broad Street, Philadelphia, PA 19140, USA

    Department of Physiology, Temple University School of Medicine, 3500 N. Broad Street, Philadelphia, PA 19140, USA
    Search for articles by this author

      Abstract

      Objective

      The Max-interacting protein Mnt is a transcriptional repressor that can antagonize the transcriptional and proliferation-related activities of Myc. Here, we tested the hypothesis that Mnt is a negative regulator of pathological vascular remodeling.

      Methods

      Adenovirus encoding Mnt or control GFP was infected to cultured rat vascular smooth muscle cells (VSMC) and carotid arteries after a balloon angioplasty.

      Results

      In VSMC, adenoviral gene transfer of Mnt suppressed angiotensin II-induced protein expression of early growth response protein-1 (Egr1) and its promoter activation. Mnt adenovirus did not interfere with upstream signaling of angiotensin II. Angiotensin II-induced protein accumulation in VSMC was inhibited by Mnt adenovirus. Mnt adenovirus also inhibited platelet-derived growth factor-induced VSMC proliferation. Moreover, Mnt adenovirus prevented neointima formation in response to arterial injury. The adenoviral Mnt gene transfer also prevented Egr1 induction in neointima.

      Conclusion

      These data identify Mnt as a previously unrecognized negative regulator of pathological vascular remodeling.

      Keywords

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