B-myb represses vascular smooth muscle cell collagen gene expression and inhibits neointima formation after arterial injury
B-myb represses vascular smooth muscle cell collagen gene expression and inhibits neointima formation after arterial injury
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DOI：
10.1161/01.atv.0000139010.71779.f3
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发表时间：
2004-09-01
影响因子：
8.7
通讯作者：
Sonenshein, GE
中科院分区：
文献类型：
--
作者：
Hofmann, CS;Sullivan, CP;Sonenshein, GE
Objectives-The function of B-Myb，a negative regulator of vascular smooth muscle cell（SMC）matrix gene transcription，was analyzed in the vasculination.Methods and Results -小鼠中的人B-myb基因由基底巨细胞病毒启动子驱动，并确定了3个创始人。小鼠似乎发育正常，人B-myb在睾丸中表达。与野生型（WT）动物相比，成年转基因动物的乳腺中总B-Myb水平升高，并与α 1（I）胶原mRNA表达呈负相关。然而，新生儿WT和转基因乳腺癌显示出相当的α 1（I）胶原mRNA水平，可能是由于细胞周期蛋白A水平升高，从而消除了B-Myb的抑制。成年转基因动物的主动脉SMC显示α 1（I）胶原mRNA水平降低。为了检查B-Myb在血管损伤后的作用，使动物经受股动脉剥脱，其诱导富含SMC的病变形成。新生内膜形成和管腔狭窄的显着减少，观察到在动脉中的B-myb转基因小鼠与WT 4 weeks after injury.Conclusions -数据表明，B-Myb，抑制基质基因表达在成人血管壁，减少血管损伤后新生内膜形成。
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 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.