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

British Journal of Pharmacology
Jeannette Rudzitis-AuthMatthias W Laschke

Abstract

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. 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. 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. Inhibition of EphB4 signalling suppresses the vascularisation and growth of en...Continue Reading

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Citations

Aug 8, 2020·Klinicheskaia laboratornaia diagnostika·R V Ukrainets, Yulia Sergeevna Korneva
Nov 7, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Christin NeuberJens Pietzsch
Jun 30, 2021·British Journal of Pharmacology·Jeannette Rudzitis-AuthMatthias W Laschke
Aug 28, 2021·Medical Sciences : Open Access Journal·Eberhard GrambowDaniel Strüder

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