Inhibition of Erythropoietin-producing Hepatoma Receptor B4 (EphB4) Signalling Suppresses the Vascularisation and Growth of Endometriotic Lesions

Overview

Journal Br J Pharmacol

Publisher Wiley

Specialty Pharmacology

Date 2020 Mar 8

PMID 32144768

Citations 5

Authors

Jeannette Rudzitis-Auth

Sophia A Fuss

Vivien Becker

Michael D Menger

Matthias W Laschke

Affiliations

Soon will be listed here.

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

Rudzitis-Auth J, Fuss S, Becker V, Menger M, Laschke M Br J Pharmacol. 2020; 177(14):3225-3239.

PMID: 32144768 PMC: 7312277. DOI: 10.1111/bph.15044.

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