on July 15, 2004
Published online before print July 15, 2004, doi: 10.1161/01.ATV.0000139010.71779.f3
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Submitted on May 11, 2004
Accepted on July 2, 2004
B-Myb Represses Vascular Smooth Muscle Cell Collagen Gene Expression and Inhibits Neointima Formation After Arterial Injury
Claudia S. Hofmann ;
From the Department of Biochemistry (C.S.H., C.P.S., H.-Y. J., P.J.S., P.T., B.M.S., G.E.S.), Boston University School of Medicine, Boston, Mass; and the Departments of Surgery (E.D.R.) and Medicine (I.C.), The Mount Sinai Medical Center, New York, NY.
* To whom correspondence should be addressed. E-mail: gsonensh{at}bu.edu.
Objectives--The function of B-Myb, a negative regulator of vascular smooth muscle cell (SMC) matrix gene transcription, was analyzed in the vasculature.
Methods and 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 
1(I) collagen mRNA expression. However, neonatal WT and transgenic aortas displayed comparable levels of 1(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 1(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.
Key words: Myb • collagen • cyclin A • aorta • femoral artery
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