Endothelial Cell - Pericyte Interdigitation in Angiogenesis

血管内皮生长因子(VEGF)是一种二聚体糖蛋白，能特异性增加血管通透性，刺激血管生成。最近，我们发现在N-丁基-N-(4-羟基丁基)亚硝胺(BBN)诱导的大鼠膀胱癌中有高水平的血管内皮生长因子和血管内皮生长因子mRNA的表达，并且有丰富的开窗毛细血管。我们推测，血管内皮细胞生长因子的表达可能参与了毛细血管开窗的诱导和维持，并观察了中和抗体对BBN诱导的大鼠膀胱癌微血管形态的影响。给药后5min，开窗内皮细胞比例和开窗数明显减少，并随时间延长继续减少，给药后10min降至最低。此后，这一比率逐渐增加，并在30分钟时恢复到其控制状态。这些结果表明，特异性的抑制血管内皮生长因子的生物活性，有效地关闭了毛细血管窗口。提示BBN诱导的大鼠膀胱癌细胞合成的血管内皮生长因子可特异性地诱导和维持肿瘤的毛细血管开窗。

Vascular endothelial growth factor (VEGF) is a dimeric glycoprotein that specifically increases vascular permeability and stimulates angiogenesis. Recently we demonstrated a high level of VEGF and VEGF mRNA expression in N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN)-induced rat bladder carcinomas with abundant fenestrated capillaries. We speculated that the expression of VEGF might be involved in the induction or maintenance of capillary fenestration, and examined ultrastructurally the morphological alteration of blood capillaries in BBN-induced rat bladder carcinoma following the administration of neutralizing antibody against VEGF. Five minutes after administration, the fenestrated endothelial cell ratio and the number of fenestrated decreased significantly, and continued to decrease with time reaching a minimum at 10 minutes after administration. The ratio thereafter gradually increased and at 30 minutes returned to its control condition. These results showed the specific inhibition of VEGF bioactivity potently induced to close the capillary fenestrations. We can suggest that VEGF synthesized by BBN-induced rat bladder carcinoma cells specifically induces and maintains the tumor capillary fenestrations.