Antiangiogenic agents are effective inhibitors of endometriosis

The Journal of Clinical Endocrinology and Metabolism
M L HullStephen K Smith

Abstract

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 endome...Continue Reading

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