Increase of smooth muscle cell migration and of intimal hyperplasia in mice lacking the alpha/beta hydrolase domain containing 2 gene.

Increase of smooth muscle cell migration and of intimal hyperplasia in mice lacking the alpha/beta hydrolase domain containing 2 gene.
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DOI:
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发表时间:
2005
影响因子:
3.1
通讯作者:
K. Miyata;Y. Oike;Takayuki Hoshii;H. Maekawa;H. Ogawa;T. Suda;K. Araki;K. Yamamura
K. Miyata;Y. Oike;Takayuki Hoshii;H. Maekawa;H. Ogawa;T. Suda;K. Araki;K. Yamamura
中科院分区:
生物学4区
文献类型:
--
作者:
K. Miyata;Y. Oike;Takayuki Hoshii;H. Maekawa;H. Ogawa;T. Suda;K. Araki;K. Yamamura

文献摘要

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动脉粥样硬化的发生涉及多个步骤,包括血管平滑肌细胞(SMC)的迁移。为了发现参与这些步骤的基因,我们筛选了在胚胎发育过程中利用X-Gal染色的可交换基因陷阱方法建立的突变小鼠系。其中一个品系在胚胎期(E)12.5天时,卵黄囊的卵黄血管中有较强的报告基因表达。将TRAP载体插入含有2(Abhd2)基因的α/β水解酶结构域的第5内含子,结果表明该基因在成年小鼠血管和非血管平滑肌细胞中均有表达。尽管纯合子突变小鼠明显正常,但与野生型小鼠相比,纯合子突变小鼠外植体SMC培养中的SMC迁移增强,并在放置袖带后出现明显的内膜增生。我们的结果表明,Abhd2参与了SMC的迁移和血管SMC的新生内膜增厚。
Multiple steps, including the migration of vascular smooth muscle cells (SMCs), are involved in the pathogenesis of atherosclerosis. To discover genes which are involved in these steps, we screened mutant mouse lines established by the exchangeable gene trap method utilizing X-gal staining during their embryonic development. One of these lines showed strong reporter gene expression in the vitelline vessels of yolk sacs at embryonic day (E) 12.5. The trap vector was inserted into the fifth intron of alpha/beta hydrolase domain containing 2 (Abhd2) gene which was shown to be expressed in vascular and non-vascular SMCs of adult mice. Although homozygous mutant mice were apparently normal, enhanced SMC migration in the explants SMCs culture and marked intimal hyperplasia after cuff placement were observed in homozygous mice in comparison with wild-type mice. Our results show that Abhd2 is involved in SMC migration and neointimal thickening on vascular SMCs.