Antiangiogenesis therapy for endometriosis.
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.
Department of Obstetrics and Gynecology, Research Institute for Growth and Development, Maastricht University and University Hospital, 6202 AZ Maastricht, The Netherlands.
Annemiek W
AW
Nap
Arjan W
AW
Griffioen
Gerard A J
GA
Dunselman
Jessica C A
JC
Bouma-Ter Steege
Victor L J L
VL
Thijssen
Johannes L H
JL
Evers
Patrick G
PG
Groothuis
D000328:Adult; D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D003510:Cyclohexanes; D004715:Endometriosis / Q000188:drug therapy* / Q000473:pathology; D004717:Endometrium / Q000098:blood supply / Q000473:pathology; D043169:Endostatins / Q000494:pharmacology; D005260:Female; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009389:Neovascularization, Pathologic / Q000188:drug therapy* / Q000473:pathology; D000077609:O-(Chloroacetylcarbamoyl)fumagillol; D010455:Peptides; D011506:Proteins / Q000494:pharmacology; D012717:Sesquiterpenes / Q000494:pharmacology*
D020533:Angiogenesis Inhibitors; D003510:Cyclohexanes; D043169:Endostatins; D010455:Peptides; D011506:Proteins; D012717:Sesquiterpenes; C111993:betapep-25 protein, synthetic; D000077609:O-(Chloroacetylcarbamoyl)fumagillol