Inhibition of erythropoietin‐producing hepatoma receptor B4 (EphB4) signalling suppresses the vascularisation and growth of endometriotic lesions

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EphB4 inhibition with NVP-BHG712 suppressed angiogenesis and stromal cell proliferation, reducing vascularization and growth of experimentally induced endometriotic lesions in mice.

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Abstract

BACKGROUND AND PURPOSE: The development of endometriotic lesions is crucially dependent on the formation of new blood vessels. In the present study, we analysed whether this process is regulated by erythropoietin-producing hepatoma receptor B4 (EphB4) signalling. EXPERIMENTAL APPROACH: We first assessed the anti-angiogenic action of the EphB4 inhibitor NVP-BHG712 in different in vitro angiogenesis assays. Then, endometriotic lesions were surgically induced in the dorsal skinfold chamber and peritoneal cavity of NVP-BHG712- or vehicle-treated BALB/c mice. This allowed to study the effect of EphB4 inhibition on their vascularisation and growth by means of intravital fluorescence microscopy, high-resolution ultrasound imaging, histology and immunohistochemistry. KEY RESULTS: Non-cytotoxic doses of NVP-BHG712 suppressed the migration, tube formation and sprouting activity of both human dermal microvascular endothelial cells (HDMEC) and mouse aortic rings. Accordingly, we also detected a lower blood vessel density in NVP-BHG712-treated endometriotic lesions. This was associated with a reduced lesion growth due to a significantly lower number of proliferating stromal cells when compared to vehicle-treated controls. CONCLUSIONS AND IMPLICATIONS: Inhibition of EphB4 signalling suppresses the vascularisation and growth of endometriotic lesions. Hence, EphB4 represents a promising pharmacological target for the treatment of endometriosis.

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Condition tags

mesh:D004715endometriosis

MeSH descriptors

Carcinoma, Hepatocellular Endometriosis Endometriosis Erythropoietin Liver Neoplasms Animals Endothelial Cells Female Humans Mice Mice, Inbred BALB C Neovascularization, Pathologic Neovascularization, Pathologic Receptor, EphB4

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europepmc
last seen: 2026-06-04T01:30:01.192114+00:00
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