Combined inhibition of vascular endothelial growth factor (VEGF), fibroblast growth factor and platelet-derived growth factor, but not inhibition of VEGF alone, effectively suppresses angiogenesis and vessel maturation in endometriotic lesions

M W Laschke, Matthias W. Laschke, Antje Elitzsch, A Elitzsch, Brigitte Vollmar, B Vollmar, P Vajkoczy, Peter Vajkoczy, M D Menger, MD Menger
Human Reproduction · 2005 · vol. 21(1) , pp. 262–268 · doi:10.1093/humrep/dei308 · PMID:16172144 · W2110567194
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Combined inhibition of VEGF, FGF, and PDGF significantly suppressed angiogenesis and vessel maturation in endometriotic lesions, unlike VEGF inhibition alone.

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Abstract

BACKGROUND: Angiogenesis represents the crucial step in the pathogenesis of endometriosis, because endometriotic lesions require neovascularization to establish, proliferate and invade inside the peritoneal cavity. To elucidate the role of angiogenic factors, we investigated in vivo whether blockade of vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF), and platelet-derived growth factor (PDGF) affects angiogenesis of ectopic endometrium. METHODS: Mechanically isolated endometrial fragments were transplanted into the dorsal skinfold chamber of hormonally synchronized hamsters. Subsequently, we analysed the effect of the VEGF inhibitor SU5416 and the combined VEGF, FGF and PDGF inhibitor SU6668 on angiogenesis of the ectopic endometrium over a time-period of 14 days using intravital fluorescence microscopy. RESULTS: Selective blockade of VEGF resulted in a slight reduction of microvessel density when compared to control animals. In contrast, combined inhibition of all three growth factors significantly suppressed angiogenesis of endometrial grafts, as indicated by a reduced size of the microvascular network and a decreased microvessel density. This was caused by an inhibition of blood vessel maturation. CONCLUSIONS: Vascularization of endometriotic lesions is not solely driven by VEGF, but depends on the cross-talk between VEGF, FGF and PDGF. Thus, the combined inhibition of these growth factors may represent a novel therapeutic strategy in the treatment of endometriosis.

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Condition tags

mesh:D004715endometriosis

MeSH descriptors

Endometriosis Endometrium Fibroblast Growth Factors Neovascularization, Pathologic Platelet-Derived Growth Factor Uterine Diseases Vascular Endothelial Growth Factor A Angiogenesis Inhibitors Angiogenesis Inhibitors Animals Capillaries Capillaries Capillaries Cricetinae Endometriosis Endometrium Female Fibroblast Growth Factors Indoles Indoles

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