title: A repressor protein, Mnt, is a novel negative regulator of vascular smooth muscle cell hypertrophy by angiotensin II and neointimal hyperplasia by arterial injury.
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.
  
  
  CONCLUSIONS
  These data identify Mnt as a previously unrecognized negative regulator of pathological vascular remodeling.
authors.affiliation: Cardiovascular Research Center, Temple University School of Medicine, 3500 N Broad Street, Philadelphia, PA 19140, USA.
authors.forename: Takehiko
authors.initials: T
authors.lastname: Takayanagi
authors.forename: Akito
authors.initials: A
authors.lastname: Eguchi
authors.forename: Akira
authors.initials: A
authors.lastname: Takaguri
authors.forename: Akinari
authors.initials: A
authors.lastname: Hinoki
authors.forename: Allison M
authors.initials: AM
authors.lastname: Bourne
authors.forename: Katherine J
authors.initials: KJ
authors.lastname: Elliott
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Hurlin
authors.forename: Satoru
authors.initials: S
authors.lastname: Eguchi
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000800:Angioplasty, Balloon / Q000009:adverse effects; D000804:Angiotensin II / Q000378:metabolism*; D000818:Animals; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / Q000235:genetics / Q000378:metabolism*; D020212:Carotid Artery Injuries / Q000378:metabolism* / Q000473:pathology; D049452:Green Fluorescent Proteins / Q000235:genetics; D006965:Hyperplasia / Q000378:metabolism / Q000473:pathology; D006984:Hypertrophy / Q000378:metabolism / Q000473:pathology; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000378:metabolism* / Q000473:pathology; D058426:Neointima / Q000378:metabolism* / Q000473:pathology; D061251:Primary Cell Culture; D051381:Rats; D017207:Rats, Sprague-Dawley; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D014158:Transcription, Genetic / Q000502:physiology
chemical_list: D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; C584054:Mnt protein, rat; D012097:Repressor Proteins; D000804:Angiotensin II; D049452:Green Fluorescent Proteins
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