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VEGF-A 促进鸡胚绒毛尿囊膜的出芽式血管生成。

VEGF-A promotes intussusceptive angiogenesis in the developing chicken chorioallantoic membrane.

机构信息

Institute of Anatomy, University of Bern, Bern 12, Switzerland.

出版信息

Microcirculation. 2010 Aug;17(6):447-57. doi: 10.1111/j.1549-8719.2010.00043.x.

DOI:10.1111/j.1549-8719.2010.00043.x
PMID:20690983
Abstract

OBJECTIVE

To assess the impact of vascular endothelial growth factor (VEGF) on intussusceptive angiogenesis.

METHODS AND RESULTS

Polyurethane casts of the microvasculature of chicken chorioallantoic membrane (CAM) were prepared on embryonic days (E) 8, 10, 12, and 14. At light microscopy level, minute holes (<2 microm in diameter) and hollows (>2 microm) were observed in the casts. Transmission electron microscopy disclosed the minute holes to mainly represent transluminal pillars characteristic for intussusceptive angiogenesis. The numerical density of the holes/pillars was highest at an early (E8) and a late (E12-E14) stage. Only mRNA of VEGF-A-122 and VEGF-A-166 isoforms was detected in the CAM. The transcription rate of VEGF-A mRNA peaked on E8/9 and E12, while VEGF-A protein expression increased on E8/9 and E11/12 to rapidly decrease thereafter as determined by immunoblotting. At all time points investigated, VEGF-A immunohistochemical reactivity was restricted to cells of the chorionic epithelium in direct contact to the capillary plexus. When the VEGF-R-inhibitor PTK787/ZK222584 (0.1 mg/mL) was applied on E9 CAM, the microvasculature topology on E12 was similar to that on E10.

CONCLUSIONS

The temporal course of intussusception corresponded to the expression of VEGF-A in CAM microvasculature. Inhibition of VEGF-signaling retarded intussusceptive-dependent capillary maturation. These data suggest that VEGF promotes intussusception.

摘要

目的

评估血管内皮生长因子(VEGF)对肠内性血管生成的影响。

方法和结果

在胚胎第 8、10、12 和 14 天,制备鸡绒毛尿囊膜(CAM)微血管的聚氨酯铸型。在光镜水平下,铸型中观察到微小孔(<2 微米直径)和凹陷(>2 微米)。透射电子显微镜显示,微小孔主要代表肠内性血管生成的腔内柱。孔/柱的数值密度在早期(E8)和晚期(E12-E14)最高。CAM 中仅检测到 VEGF-A-122 和 VEGF-A-166 异构体的 mRNA。VEGF-A mRNA 的转录率在 E8/9 和 E12 达到峰值,而 VEGF-A 蛋白表达在 E8/9 和 E11/12 增加,随后迅速下降,通过免疫印迹法测定。在所有研究的时间点,VEGF-A 的免疫组织化学反应性仅限于与毛细血管丛直接接触的绒毛膜上皮细胞。当应用 VEGF-R 抑制剂 PTK787/ZK222584(0.1 mg/mL)于 E9 CAM 时,E12 的微血管拓扑结构与 E10 相似。

结论

肠内性的时间过程与 CAM 微血管中 VEGF-A 的表达相对应。VEGF 信号的抑制延迟了肠内性依赖的毛细血管成熟。这些数据表明 VEGF 促进肠内性。

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