Published online before print July 15, 2004, doi: 10.1161/01.ATV.0000139010.71779.f3
© 2004 American Heart Association, Inc.
Vascular Biology |
B-Myb Represses Vascular Smooth Muscle Cell Collagen Gene Expression and Inhibits Neointima Formation After Arterial Injury
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.
Correspondence to Gail E. Sonenshein, Department of Biochemistry, Boston University School of Medicine, 715 Albany St, Boston, MA 02118. 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.
To analyze B-Myb function in the vasculature, mice overexpressing B-myb were generated. Neonates displayed normal 1(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.
Key Words: Myb • collagen • cyclin A • aorta • femoral artery
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