B-Myb represses vascular smooth muscle cell collagen gene expression and inhibits neointima formation after arterial injury.
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.
Hofmann
Claudia S
CS
Department of Biochemistry, Boston University School of Medicine, 715 Albany St, Boston, MA 02118, USA.
Sullivan
Christopher P
CP
Jiang
Hao-Yuan
HY
Stone
Phillip J
PJ
Toselli
Paul
P
Reis
Ernane D
ED
Chereshnev
Igor
I
Schreiber
Barbara M
BM
Sonenshein
Gail E
GE
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*
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