Arteriolar and venular patterning in retinas of mice selectively expressing VEGF isoforms

Arteriolar and venular patterning in retinas of mice selectively expressing VEGF isoforms
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DOI:
10.1172/jci0214362
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发表时间:
2002-02-01
影响因子:
15.9
通讯作者:
D'Amore, PA
D'Amore, PA
中科院分区:
医学1区
文献类型:
--
作者:
Stalmans, I;Ng, YS;D'Amore, PA

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鼠VEGF基因可选择性地转录以产生VEGF(120)、VEGF(164)和VEGF(188)同种型,它们在结合硫酸乙酰肝素和神经纤毛蛋白-1和刺激内皮生长的潜力方面不同。在这里,他们在视网膜血管发育中的作用进行了研究,在小鼠选择性表达单一亚型。VEGF(164/164)小鼠是正常的、健康的,并且具有正常的视网膜血管生成。相比之下,VEGF(120/120)小鼠在血管生长和模式方面表现出严重缺陷,而VEGF(188/188)小鼠表现出正常的小静脉生长,但动脉发育受损。值得注意的是,neuropilin-1,VEGF 164的受体,主要在视网膜小动脉中表达。这些发现揭示了不同的VEGF亚型在视网膜血管形成和动脉发育中的不同作用。
The murine VEGF gene is alternatively transcribed to yield the VEGF(120), VEGF(164), and VEGF(188) isoforms, which differ in their potential to bind to heparan sulfate and neuropilin-1 and to stimulate endothelial growth. Here, their role in retinal vascular development was studied in mice selectively expressing single isoforms. VEGF(164/164) mice were normal, healthy, and had normal retinal angiogenesis. In contrast, VEGF(120/120) Mice exhibited severe defects in vascular outgrowth and patterning, whereas VEGF(188/188) mice displayed normal venular outgrowth but impaired arterial development. It is noteworthy that neuropilin-1, a receptor for VEGF164, was predominantly expressed in retinal arterioles. These findings reveal distinct roles of the various VEGF isoforms in vascular patterning and arterial development in the retina.