VEGF induces hyperpermeability by a direct action on endothelial cells
VEGF induces hyperpermeability by a direct action on endothelial cells
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DOI：
10.1152/ajplung.1998.274.5.l678
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发表时间：
1998-05-01
影响因子：
4.9
通讯作者：
Suttorp, N
中科院分区：
文献类型：
--
作者：
Hippenstiel, S;Krüll, M;Suttorp, N
血管内皮生长因子（VEGF）是血管和血管生成的关键调节因子。早期的研究表明，在皮肤试验中VEGF具有增加通透性的作用，因此它的另一个名字是血管通透性因子。我们想知道VEGF诱导的高通透性是否是VEGF对内皮细胞的直接影响，并在体外系统中研究了人和猪内皮细胞单层的通透性。VEGF可使水导率提高20倍，同时降低白蛋白反射系数。这种效应发生在延迟150分钟后，尽管vegf诱导的早期内皮细胞活化在5分钟内增强了肌醇磷酸盐积累，并在15分钟内增加了p -选择素表达。血小板衍生生长因子和粒细胞-巨噬细胞集落刺激因子这两种内皮细胞非特异性裂丝原也刺激磷脂酰肌醇代谢和p -选择素的表达；然而，它们没有任何效果；内皮通透性。人内皮单层细胞内环核苷酸水平的增加可消除vegf诱导的内皮细胞高通透性。综上所述，VEGF通过直接作用于内皮细胞而增加内皮细胞的通透性。基于内皮细胞被生长因子激活的模式，VEGF似乎是一种独特的刺激。
Vascular endothelial growth factor (VEGF) is a key regulator of vasculo- and angiogenesis. Earlier studies demonstrated a permeability-increasing effect of VEGF in skin tests, leading to its other name, vascular permeability factor. We wondered whether VEGF-induced hyperpermeability was a direct effect of VEGF on endothelial cells and studied the permeability of human and porcine endothelial cell monolayers in a well-characterized in vitro system. VEGF increased the hydraulic conductivity up to 20-fold and simultaneously decreased the albumin reflection coefficient. This effect occurred after a delay of 150 min, although VEGF-induced early endothelial cell activation was verified by enhanced inositol phosphate accumulation within 5 min and increased P-selectin expression within 15 min. Platelet-derived growth factor and granulocyte-macrophage colony-stimulating factor, two endothelial cell nonspecific mitogens, also stimulated phosphatidylinositol metabolism and P-selectin expression; however, they had no effect; on endothelial permeability. The increase in intracellular cyclic nucleotide levels of human endothelial monolayers abolished VEGF-induced endothelial hyperpermeability. In summary, VEGF increased endothelial permeability by a direct action on endothelial cells. Based on the pattern of endothelial cell activation by growth factors, VEGF appears to be a unique stimulus.