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Project

BMP signalling in endothelial function and dysfunction

The inner walls of blood and lymphatic vessels are lined by endothelial cells (ECs). These cells show important heterogeneity among different organs and vessel types. Understanding how this heterogeneity is acquired is key to explain why vascular diseases develop in an organ- and vessel type-specific manner. BMP signalling and flow dynamics regulate EC heterogeneity and plasticity, but the precise mechanisms remain incompletely understood. Our preliminary results from a 2-year C1-project show that BMP effector proteins regulate EC heterogeneity in healthy vessels in different organs. Now, we want to investigate these processes in (i) transgenic animal disease models, i.e. liver fibrosis and lymphedema; (ii) two new mouse strains that track BMP effector activity; (iii) early arterial specification and iv) altered flow conditions. Results obtained in mice will be cross-validated in tissue biopsies from human patients. We aim to contribute to unravelling mechanisms of (impaired) EC heterogeneity that should allow designing tailor-made vessel normalisation and regeneration strategies, a major challenge in curing vessel-related disease.
Date:1 Oct 2019 →  30 Sep 2023
Keywords:Vascular disease, Endothelial heterogeneity, BMP signalling, Transgenic mouse models, Haemodynamics
Disciplines:Vascular diseases