title: B-Myb represses vascular smooth muscle cell collagen gene expression and inhibits neointima formation after arterial injury.
abstract: OBJECTIVE
  The function of B-Myb, a negative regulator of vascular smooth muscle cell (SMC) matrix gene transcription, was analyzed in the vasculature.
  
  
  RESULTS
  Mice were generated in which the human B-myb gene was driven by the basal cytomegalovirus promoter, and 3 founders were identified. Mice appeared to develop normally, and human B-myb was expressed in the aortas. Total B-Myb levels were elevated in aortas of adult transgenic versus wild-type (WT) animals and varied inversely with alpha1(I) collagen mRNA expression. However, neonatal WT and transgenic aortas displayed comparable levels of alpha1(I) collagen mRNA, likely resulting from elevated levels of cyclin A, which ablated repression by B-Myb. Aortic SMCs from adult transgenic animals displayed decreased alpha1(I) collagen mRNA levels. To examine the role of B-Myb after vascular injury, animals were subjected to femoral artery denudation, which induces SMC-rich lesion formation. A dramatic reduction in neointima formation and lumenal narrowing was observed in arteries of B-myb transgenic versus WT mice 4 weeks after injury.
  
  
  CONCLUSIONS
  Data indicate that B-Myb, which inhibits matrix gene expression in the adult vessel wall, reduces neointima formation after vascular injury. To analyze B-Myb function in the vasculature, mice overexpressing B-myb were generated. Neonates displayed normal alpha1(I) collagen mRNA levels, whereas adults expressed decreased collagen mRNA in aortas and isolated vascular SMCs. On femoral artery denudation, neointima formation was dramatically reduced in B-myb transgenic mice.
authors.affiliation: Department of Biochemistry, Boston University School of Medicine, 715 Albany St, Boston, MA 02118, USA.
authors.forename: Claudia S
authors.initials: CS
authors.lastname: Hofmann
authors.forename: Christopher P
authors.initials: CP
authors.lastname: Sullivan
authors.forename: Hao-Yuan
authors.initials: HY
authors.lastname: Jiang
authors.forename: Phillip J
authors.initials: PJ
authors.lastname: Stone
authors.forename: Paul
authors.initials: P
authors.lastname: Toselli
authors.forename: Ernane D
authors.initials: ED
authors.lastname: Reis
authors.forename: Igor
authors.initials: I
authors.lastname: Chereshnev
authors.forename: Barbara M
authors.initials: BM
authors.lastname: Schreiber
authors.forename: Gail E
authors.initials: GE
authors.lastname: Sonenshein
mesh_terms: D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D001011:Aorta / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D003094:Collagen / Q000096:biosynthesis* / Q000235:genetics; D019925:Cyclin A / Q000096:biosynthesis / Q000235:genetics; D003587:Cytomegalovirus / Q000235:genetics; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D005260:Female; D005263:Femoral Artery / Q000293:injuries / Q000378:metabolism / Q000473:pathology; D005786:Gene Expression Regulation; D006801:Humans; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009131:Muscle, Smooth, Vascular / Q000378:metabolism* / Q000473:pathology; D032389:Myocytes, Smooth Muscle / Q000378:metabolism* / Q000473:pathology; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000096:biosynthesis; D015534:Trans-Activators / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D019076:Transgenes; D017539:Tunica Intima / Q000473:pathology*
chemical_list: D018797:Cell Cycle Proteins; D019925:Cyclin A; D004268:DNA-Binding Proteins; C064352:MYBL2 protein, human; C499306:Mybl2 protein, mouse; D012333:RNA, Messenger; D015534:Trans-Activators; D003094:Collagen