Angiotensinogen impairs angiogenesis in the chick chorioallantoic membrane
Angiotensinogen impairs angiogenesis in the chick chorioallantoic membrane
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DOI：
10.1007/s00109-006-0141-6
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发表时间：
2007-05-01
影响因子：
4.7
通讯作者：
Gasc, Jean-Marie
中科院分区：
文献类型：
--
作者：
Brand, Marcus;Lamande, Noel;Gasc, Jean-Marie
血管紧张素原与丝氨酸蛋白酶抑制剂（serpin）家族的其他成员共享抗血管生成特性。血管紧张素原在体外抑制内皮细胞增殖，在鸡胚绒毛尿囊膜试验中是卵内抗血管生成的。通过将纯化的人血管紧张素原或产生重组血管紧张素原的中国仓鼠卵巢细胞应用于发育中的绒毛尿囊膜上，研究了血管紧张素原的细胞作用模式。血管密度的控制和血管紧张素原治疗领域的定量使用接骨木凝集素，一个特定的内皮细胞标志物。通过应用纯化的血管紧张素原或血管紧张素原产生的中国仓鼠卵巢细胞进行血管紧张素原处理48小时后，与对照切片相比，中胚层血管密度降低了70%。血管紧张素原治疗诱导强烈减少绒毛尿囊膜血管内皮细胞增殖，如溴脱氧尿苷掺入所示。局部血管紧张素原治疗后2天，转移酶介导的脱氧尿苷三磷酸缺口末端标记法检测中胚层血管内皮细胞凋亡增加。通过原位杂交评估，血管紧张素原并没有改变主要血管生长因子及其受体的基因表达模式。因此，血管紧张素原通过诱导细胞凋亡和降低内皮细胞增殖而损害血管生成，而不改变血管生长因子的表达水平。
Angiotensinogen shares with other members of the serine protease inhibitor (serpin) family antiangiogenic properties. Angiotensinogen inhibits in vitro endothelial cell proliferation, and is antiangiogenic in ovo in the chick chorioallantoic membrane assay. The cellular mode of action of angiotensinogen has been studied by applying purified human angiotensinogen or Chinese hamster ovary cells producing recombinant angiotensinogen onto the developing chorioallantoic membrane. Vessel density of the control and angiotensinogen-treated areas was quantitated by using Sambucus nigra lectin, a specific endothelial cell marker. After 48 h of angiotensinogen treatment by either applying purified angiotensinogen or angiotensinogen-producing Chinese hamster ovary cells, there was a 70% decrease in mesodermic vessel density in comparison to the control sections. Angiotensinogen treatment induced a strong decrease in endothelial cell proliferation of the chorioallantoic membrane vasculature, as shown by incorporation of bromo-deoxyuridine. Two days after local angiotensinogen treatment, increased apoptosis of endothelial cells of mesodermal blood vessels was detected by transferase-mediated deoxyuridine triphosphate nick end labeling assay. As assessed by in situ hybridization, the gene expression pattern of the main vascular growth factors and their receptors was not altered by angiotensinogen. Angiotensinogen, therefore, impairs angiogenesis without altering the expression level of vascular growth factors through the induction of apoptosis and decreased endothelial cell proliferation.