Antiangiogenic agents are effective inhibitors of endometriosis.
Endometriosis is a disease in which the lining of the uterus (endometrium), shed at the time of menstruation, becomes established at sites such as the peritoneum and ovaries. These explants develop a rich blood supply that enables them to survive and grow. We hypothesized that inhibitors of angiogenesis would prevent this growth by disrupting sensitive vessels supplying endometriotic lesions. Vessels sensitive to angiogenic antagonism have few associations with pericyte cells. The vessels supplying human endometriotic lesions were immunohistochemically characterized and found to be predominantly pericyte free. A model in which human endometrium is implanted into nude mice was used to test the effects of two antagonists of the angiogenic growth factor, vascular endothelial cell growth factor A. Soluble truncated receptor (flt-1; P = 0.002) and an affinity-purified antibody to human vascular endothelial cell growth factor A (P = 0.03) significantly inhibited the growth of nude mouse explants. Pericyte-free vessels were shown to supply endometrial lesions in nude mice and were disrupted in lesions taken from soluble flt-1-treated mice. In summary, antiangiogenic agents inhibited the growth of explants in an in vivo model of endometriosis by disrupting the vascular supply, and this effect is likely to apply to the human disease. These findings suggest that antiangiogenic agents may provide a novel therapeutic approach for the treatment of endometriosis.
Hull
M Louise
ML
Department of Pathology, Reproductive Molecular Research Group, Cambridge, United Kingdom CB2 1QP. mlh30@cam.ac.uk
Charnock-Jones
D Stephen
DS
Chan
Clement L K
CL
Bruner-Tran
Kaylon L
KL
Osteen
Kevin G
KG
Tom
Brian D M
BD
Fan
Tai-Ping D
TP
Smith
Stephen K
SK
D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D001808:Blood Vessels / Q000473:pathology; D004715:Endometriosis / Q000517:prevention & control*; D004717:Endometrium / Q000098:blood supply; D016228:Endothelial Growth Factors / Q000037:antagonists & inhibitors / Q000276:immunology; D005260:Female; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000276:immunology; D008222:Lymphokines / Q000276:immunology; D051379:Mice; D008819:Mice, Nude; D051381:Rats; D017208:Rats, Wistar; D012995:Solubility; D042461:Vascular Endothelial Growth Factor A; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000502:physiology; D042442:Vascular Endothelial Growth Factors
D020533:Angiogenesis Inhibitors; D000906:Antibodies; D016228:Endothelial Growth Factors; D036341:Intercellular Signaling Peptides and Proteins; D008222:Lymphokines; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D040281:Vascular Endothelial Growth Factor Receptor-1