Vascular endothelial growth factor is produced by peritoneal fluid macrophages in endometriosis and is regulated by ovarian steroids.

J McLaren, A. G. Prentice, A Prentice, D S Charnock-Jones, D. Stephen Charnock‐Jones, Stephanie A. Millican, S A Millican, Karin H. Müller, K H Müller, A M Sharkey, Andrew Sharkey, S K Smith
The Journal of clinical investigation · 1996 · vol. 98(2) , pp. 482–489 · doi:10.1172/jci118815 · PMID:8755660 · PMC507453 · W2058587734
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⚙ AI-generated summary by claude@2026-06, 2026-06-09 ⓘ

Peritoneal fluid macrophages in endometriosis produce vascular endothelial growth factor, which is regulated by ovarian steroids and contributes to angiogenesis.

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⚙ AI-generated deep summary by claude@2026-06, 2026-06-09 ⓘ

This study investigated where vascular endothelial growth factor (VEGF) is expressed and how it is regulated in endometriosis, focusing on macrophages in ectopic endometrium and peritoneal fluid. VEGF immunoreactivity was found in tissue macrophages in ectopic lesions and in activated peritoneal fluid macrophages, with macrophage activation highest in women with endometriosis; conditioned media from these macrophages increased endothelial cell proliferation in a VEGF-dependent manner. The authors reported that peritoneal fluid macrophages secreted VEGF in response to ovarian steroids, with enhanced secretion after lipopolysaccharide activation, and detected steroid-hormone receptors as well as VEGF receptors (flt and KDR), including higher KDR expression and VEGF-driven migration in endometriosis, particularly in the luteal phase. This paper is centrally about endometriosis — it identifies activated macrophages as a major VEGF source and shows direct regulation by ovarian steroids in endometriosis.

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Abstract

Angiogenesis is important in the pathophysiology of endometriosis, a condition characterized by implantation of ectopic endometrium in the peritoneal cavity. Vascular endothelial growth factor (VEGF) is a potent angiogenic factor involved in physiological and pathological angiogenesis, and elevated levels of VEGF are found in peritoneal fluid of patients with endometriosis. Our aim was to investigate the site of expression and regulation of VEGF in endometriosis. VEGF immunoreactivity was found in tissue macrophages present in ectopic endometrium and in activated peritoneal fluid macrophages. Macrophage activation was highest in women with endometriosis, and media conditioned by peritoneal fluid macrophages from these women caused a VEGF-dependent increase in endothelial cell proliferation above that seen from normal women. Peritoneal fluid macrophages secreted VEGF in response to ovarian steroids, and this secretion was enhanced after activation with lipopolysaccharide. Peritoneal fluid macrophages expressed receptors for steroid hormones. VEGF receptors flt and KDR (kinase domain receptor) were also detected, suggesting autocrine regulation. During the menstrual cycle, expression of flt was constant but that of KDR was increased in the luteal phase, at which time the cells migrated in response to VEGF. KDR expression and the migratory response were significantly higher in patients with endometriosis. This study demonstrates that activated macrophages are a major source of VEGF in endometriosis and that this expression is regulated directly by ovarian steroids.

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Condition tags

endometriosis

MeSH descriptors

Endometriosis Endothelial Growth Factors Endothelium, Vascular Estradiol Lymphokines Macrophages, Peritoneal Progesterone Adult Base Sequence Biological Assay Cells, Cultured Culture Media, Conditioned DNA Primers Endometriosis Endometriosis Endothelial Growth Factors Endothelial Growth Factors Endothelial Growth Factors Endothelium, Vascular Endothelium, Vascular

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