Functional ephrin-B2 expression for promotive interaction between arterial and venous vessels in postnatal neovascularization

Functional ephrin-B2 expression for promotive interaction between arterial and venous vessels in postnatal neovascularization
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DOI:
10.1161/01.cir.0000163566.07427.73
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发表时间:
2005-05-03
期刊:
影响因子:
37.8
通讯作者:
Losordo, DW
Losordo, DW
中科院分区:
医学1区
文献类型:
--
作者:
Hayashi, S;Asahara, T;Losordo, DW

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背景-Ephrin-B2是一种跨膜配体,是胚胎期动脉内皮细胞的遗传标记物,对心血管发育至关重要,但其在缺血性心血管疾病中的作用尚不清楚。在这项研究中,我们专注于功能的ephrin-B2在产后neovascularization.Methods和结果,我们发现,ephrin-B2是专门表达和显着上调后,在组织缺血的初始血管生成反应的动脉血管。在体外EC索状形成中也观察到肝配蛋白-B2的上调。有趣的是,肝配蛋白-B2在内皮细胞上的表达被促进血管生成的生长因子如血管内皮生长因子、碱性成纤维细胞生长因子和肝细胞生长因子增强,而被血管生成素-1(血管成熟因子)减弱。此外,肝配蛋白-B2丰富的环境被证明主要是通过在体内角膜微囊assay.Conclusions-Our研究表明,肝配蛋白-B2配体诱导新生血管形成静脉血管生成很可能有功能性表达血管生成动脉内皮细胞和诱导随后的促进作用,在出生后新生血管形成的静脉血管。
Background-Ephrin-B2, one of the transmembrane ligands, is a genetic marker of arterial endothelial cells (ECs) at embryonic stages and is essential for cardiovascular development, but its roles in ischemic cardiovascular disease are not well understood. In this study, we focused on the function of ephrin-B2 in postnatal neovascularization.Methods and Results-We found that ephrin-B2 is exclusively expressed and significantly upregulated in the arterial vasculature after the initial angiogenic responses in tissue ischemia. Upregulation of ephrin-B2 is also observed in EC cordlike formation in vitro. Interestingly, ephrin-B2 expression on ECs was enhanced by promotive angiogenic growth factors, such as vascular endothelial growth factor, basic fibroblast growth factor, and hepatocyte growth factor, whereas it was attenuated by angiopoietin-1, a factor for blood vessel maturation. Moreover, an ephrin-B2-rich environment was shown to induce neovascularization mainly through venous angiogenesis in an in vivo cornea micropocket assay.Conclusions-Our study indicates that the ephrin-B2 ligand is likely to have functional expression on angiogenic arterial ECs and induce a subsequent promotive effect on venous vessels during postnatal neovascularization.