EVEC, a novel epidermal growth factor-like repeat-containing protein upregulated in embryonic and diseased adult vasculature
EVEC, a novel epidermal growth factor-like repeat-containing protein upregulated in embryonic and diseased adult vasculature
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DOI：
10.1161/01.res.84.10.1166
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发表时间：
1999-05-28
影响因子：
20.1
通讯作者：
Olson, EN
中科院分区：
文献类型：
--
作者：
Kowal, RC;Richardson, JA;Olson, EN
血管病变的标志是血管平滑肌细胞（VSMC）从静止、收缩状态到具有更胎儿模式的基因表达的更原始、增殖表型的表型调节。使用减法杂交，以确定基因，可能会调节这一转变，我们克隆了一种新的基因命名为EVEC，其在胚胎血管系统中的表达和存在的Ca 2+结合表皮生长因子样重复的预测蛋白质结构的首字母缩略词。尽管这些重复序列是细胞外基质蛋白、原纤蛋白、纤蛋白和潜在转化生长因子β结合蛋白的特征，但EVEC最接近H411和T16/S1-5基因产物，据信后者调节静止成纤维细胞中的DNA合成。使用原位杂交，我们证明了EVEC主要表达在E11.5至E16.5小鼠胚胎发育动脉的VSMC中。在内皮细胞、软骨膜、肠以及面部和肾脏的间充质中也观察到较低水平的表达。EVEC mRNA表达在成人动脉中显著下调，除了在子宫中，其中循环血管生成继续;然而，EVEC表达在2个独立的啮齿动物血管损伤模型中重新激活。在LDL受体缺陷的人载脂蛋白B转基因小鼠的动脉粥样硬化斑块的细胞成分中以及在球囊损伤的大鼠颈动脉的中膜和新生内膜的VSMC中观察到EVEC mRNA。这些数据表明，EVEC可能发挥重要作用，在发育过程中的血管生长和成熟的调节和损伤血管的病变。
A hallmark of vascular lesions is the phenotypic modulation of vascular smooth muscle cells (VSMCs) from a quiescent, contractile state to a more primitive, proliferative phenotype with a more fetal pattern of gene expression. Using subtraction hybridization to identify genes that may regulate this transition, we cloned a novel gene named EVEC, an acronym for its expression in the embryonic vasculature and the presence of Ca2+ binding Epidermal growth factor-like repeats contained in the predicted protein structure. Although these repeats are characteristic of the extracellular matrix proteins, fibrillin, fibulin, and the latent transforming growth factor-beta binding proteins, EVEC most closely resembles the H411 and T16/S1-5 gene products, the latter of which are believed to regulate DNA synthesis in quiescent fibroblasts. Using in situ hybridization, we demonstrated that EVEC is expressed predominantly in the VSMCs of developing arteries in E11.5 through E16.5 mouse embryos. Lower levels of expression are also observed in endothelial cells, perichondrium, intestine, and mesenchyme of the face and kidney. EVEC mRNA expression is dramatically downregulated in adult arteries, except in the uterus, where cyclic angiogenesis continues; however, EVEC expression is reactivated in 2 independent rodent models of vascular injury. EVEC mRNA is observed in cellular elements of atherosclerotic plaques of LDL receptor-deficient, human apolipoprotein B transgenic mice and in VSMCs of the media and neointima of balloon-injured rat carotid arteries. These data suggest that EVEC may play an important role in the regulation of vascular growth and maturation during development and in lesions of injured vessels.