Antiangiogenic Agents Are Effective Inhibitors of Endometriosis

M Louise Hull, D Stephen Charnock-Jones, D. Stephen Charnock‐Jones, Clement L K Chan, Kaylon L Bruner-Tran, Kaylon L. Bruner‐Tran, Kevin G Osteen, Brian D M Tom, Tai-Ping D Fan, Tai‐Ping D. Fan, S. K. Smith, Stephen K Smith
The Journal of clinical endocrinology and metabolism · 2003 · vol. 88(6) , pp. 2889–2899 · doi:10.1210/jc.2002-021912 · PMID:12788903 · W2056951482
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Antiangiogenic agents inhibited endometriotic lesion growth in a nude mouse model by disrupting the pericyte-free vascular supply, suggesting a potential therapeutic approach for endometriosis.

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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 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.

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Condition tags

endometriosis

MeSH descriptors

Angiogenesis Inhibitors Endometriosis Angiogenesis Inhibitors Animals Antibodies Antibodies Blood Vessels Blood Vessels Endometriosis Endometrium Endometrium Endothelial Growth Factors Endothelial Growth Factors Endothelial Growth Factors Female Humans Intercellular Signaling Peptides and Proteins Intercellular Signaling Peptides and Proteins Lymphokines Lymphokines

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