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|Title:||Inhibition of erythropoietin-producing hepatoma receptor B4 (EphB4) signalling suppresses the vascularisation and growth of endometriotic lesions|
Fuß, Sophia A.
Menger, Michael D.
Laschke, Matthias W.
|Title:||British Journal of Pharmacology|
|Year of Publication:||2020|
|DDC notations:||610 Medicine and health|
|Publikation type:||Journal Article|
|Abstract:||Background and Purpose:The development of endometriotic lesions is cruciallydependent on the formation of new blood vessels. In the present study, we analysedwhether this process is regulated by erythropoietin-producing hepatoma receptor B4(EphB4) signalling.Experimental Approach:We first assessed the anti-angiogenic action of the EphB4inhibitor NVP-BHG712 in different in vitro angiogenesis assays. Then, endometrioticlesions were surgically induced in the dorsal skinfold chamber and peritonealcavity of NVP-BHG712- or vehicle-treated BALB/c mice. This allowed to study theeffect of EphB4 inhibition on their vascularisation and growth by means of intravitalfluorescence microscopy, high-resolution ultrasound imaging, histology andimmunohistochemistry.Key Results:Non-cytotoxic doses of NVP-BHG712 suppressed the migration, tubeformation and sprouting activity of both human dermal microvascular endothelialcells (HDMEC) and mouse aortic rings. Accordingly, we also detected a lower bloodvessel density in NVP-BHG712-treated endometriotic lesions. This was associatedwith a reduced lesion growth due to a significantly lower number of proliferatingstromal cells when compared to vehicle-treated controls.Conclusions and Implications:Inhibition of EphB4 signalling suppresses thevascularisation and growth of endometriotic lesions. Hence, EphB4 represents apromising pharmacological target for the treatment of endometriosis.|
|DOI of the first publication:||10.1111/bph.15044|
|URL of the first publication:||https://bpspubs.onlinelibrary.wiley.com/doi/10.1111/bph.15044|
|Link to this record:||urn:nbn:de:bsz:291--ds-363405|
|Date of registration:||2-Jun-2022|
|Faculty:||M - Medizinische Fakultät|
|Department:||M - Chirurgie|
|Professorship:||M - Prof. Dr. Michael D. Menger|
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