Antiangiogenesis therapy for endometriosis
Antiangiogenesis therapy for endometriosis
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DOI：
10.1210/jc.2003-031406
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发表时间：
2004-03-01
影响因子：
5.8
通讯作者：
Groothuis, PG
中科院分区：
文献类型：
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作者：
Nap, AW;Griffioen, AW;Groothuis, PG
众所周知，血管生成对子宫内膜异位症的发展至关重要。然而，在治疗子宫内膜异位症患者时，仅仅预防子宫内膜异位症病变发展是不够的。必须制定旨在干扰已形成病变的治疗方案。在这项研究中，我们评估了血管抑制疗法对血管生成的抑制是否也能有效地对抗子宫内膜异位症的维持。我们在裸鼠模型中评估了血管抑制化合物抗人血管内皮生长因子、TNP-470、内皮抑素和心绞痛对已建立的子宫内膜异位症病变生长的影响。我们发现人子宫内膜在增殖性子宫内膜中具有高度的血管生成能力，血管内皮生长因子- a是最重要的血管生成促进因子。血管抑制剂显著降低微血管密度和已建立的子宫内膜异位症病变的数量。在其余病变中，对照组和治疗组小鼠周细胞保护血管的数量没有差异；然而，在血管抑制剂组中，未受保护的血管数量明显减少。我们的数据表明，血管生成抑制剂通过抑制血管生成有效地干扰子宫内膜异位症的维持和生长。这表明血管抑制剂的应用可能是治疗子宫内膜异位症的有效方法。
It is known that angiogenesis is of pivotal importance for the development of endometriosis. However, in the treatment of endometriosis patients, prevention of endometriosis lesion development only will not be sufficient as a therapy. Treatment options, aimed at interfering with established lesions, have to be developed. In this study we evaluated whether inhibition of angiogenesis by angiostatic therapy is also effective in antagonizing the sustentation of endometriosis. We evaluated the effect of the angiostatic compounds antihuman vascular endothelial growth factor, TNP-470, endostatin, and anginex on the growth of established endometriosis lesions in the nude mouse model. We show that human endometrium in the proliferative endometrium is highly angiogenic and that vascular endothelial growth factor-A is the most important angiogenesis promotory factor. The angiostatic compounds significantly decreased microvessel densities and the number of established endometriosis lesions. In the remaining lesions, the number of pericyte-protected vessels is not different in control and treated mice; however, the number of unprotected vessels was significantly reduced in the groups treated with the angiostatic agents. Our data demonstrate that inhibitors of angiogenesis effectively interfere with the maintenance and growth of endometriosis by inhibiting angiogenesis. This suggests that the use of angiostatic agents may be promising as a therapy for endometriosis.