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Department of Obstetrics and Gynecology (A.W.N., G.A.J.D., J.L.H.E., P.G.G.) and Angiogenesis Laboratory, Departments of Pathology and Internal Medicine (A.W.G., J.C.A.B.-T.S., V.L.J.L.T.), Research Institute for Growth and Development, Maastricht University and University Hospital, 6202 AZ Maastricht, The Netherlands
Address all correspondence and requests for reprints to: Dr. Patrick G. Groothuis, Department of Obstetrics and Gynecology, P.O. Box 5800, 6202 AZ Maastricht, The Netherlands. E-mail: patrick.groothuis{at}path.unimaas.nl.
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.
This work was supported by an unrestricted grant from Ferring BV (Hoofddorp, The Netherlands; to A.W.N.) and by the Stichting Technische Wetenschappen (Grant MPG-5456; to A.W.G.).
Abbreviations: CD, Cycle day; EC, endothelial cell; H&E, hematoxylin and eosin; hVEGF, human VEGF; 
SMA, -smooth muscle actin; VEGF, vascular endothelial growth factor; VEGF-R, VEGF receptor; vWF, von Willebrand factor.
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