B-Myb Represses Vascular Smooth Muscle Cell Collagen Gene Expression and Inhibits Neointima Formation After Arterial Injury

• Published in: Arteriosclerosis, thrombosis, and vascular biology Vol. 24; no. 9; pp. 1608 - 1613
• Main Authors: Hofmann, Claudia S, Sullivan, Christopher P, Jiang, Hao-Yuan, Stone, Phillip J, Toselli, Paul, Reis, Ernane D, Chereshnev, Igor, Schreiber, Barbara M, Sonenshein, Gail E
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Heart Association, Inc 01-09-2004; Hagerstown, MD Lippincott
• Subjects: Age Factors; Animals; Animals, Newborn; Aorta - metabolism; Atherosclerosis (general aspects, experimental research); Biological and medical sciences; Blood and lymphatic vessels; Cardiology. Vascular system; Cell Cycle Proteins - biosynthesis; Cell Cycle Proteins - genetics; Cell Cycle Proteins - physiology; Collagen - biosynthesis; Collagen - genetics; Cyclin A - biosynthesis; Cyclin A - genetics; Cytomegalovirus - genetics; Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous; DNA-Binding Proteins - biosynthesis; DNA-Binding Proteins - genetics; DNA-Binding Proteins - physiology; Female; Femoral Artery - injuries; Femoral Artery - metabolism; Femoral Artery - pathology; Gene Expression Regulation; Human cytomegalovirus; Humans; Male; Medical sciences; Mice; Mice, Transgenic; Muscle, Smooth, Vascular - metabolism; Muscle, Smooth, Vascular - pathology; Myocytes, Smooth Muscle - metabolism; Myocytes, Smooth Muscle - pathology; Promoter Regions, Genetic; RNA, Messenger - biosynthesis; Trans-Activators - biosynthesis; Trans-Activators - genetics; Trans-Activators - physiology; Transgenes; Tunica Intima - pathology; Femoral artery; Glycoprotein; Cyclin; Cardiovascular disease; Smooth muscle; Gene expression; Vascular disease; Blood vessel; Collagen; Atherosclerosis; Myb; Aorta; Circulatory system; cyclin A
• ISSN: 1079-5642; 1524-4636
• DOI: 10.1161/01.ATV.0000139010.71779.f3

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 α1(I) collagen mRNA expression. However, neonatal WT and transgenic aortas displayed comparable levels of α1(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 α1(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.