Adaptive and maladaptive endothelial cell dynamics during blood flow-driven vascular patterning — ADAPT2FLOW
Funding Agency European Commission
Funding Programme Horizon 2020
Project reference 842498
Start date 2019.10.01
Duration 24 months
Total investment EUR 147 815,04
Project Beneficiaries Instituto de Medicina Molecular João Lobo Antunes (iMM), Portugal;
Researcher Marie Ouarné
Supervisor Cláudio Franco
The formation of a functional patterned vascular network (well-defined arteries, veins, and capillaries) is essential for blood vessel functioning and global health. Several human vascular disorders arise from the mis-patterning of blood vessels, such as arteriovenous malformations, aneurysms, and diabetic retinopathy. Blood flow is recognized as the main inducer for vascular patterning, yet very little is known about the molecular mechanisms that vascular patterning. Endothelial cells (the cells bordering vessels) polarize and migrate against the blood flow direction. Yet, how this behavior contributes to the overall process of vascular patterning is completely unknown.
It is essential to decipher how endothelial cell polarization and migration against blood flow contributes to vascular patterning as it will provide leads to produce new treatments. Indeed, those new therapies will allow improving the recovery of vascular diseases and might help to prevent some to occur like strokes in predisposed patients.
This project aimed to study the dynamics of endothelial cells in vascular patterning during development, normal blood vessel functioning, and disease. Thanks to this action, we developed new tools to study endothelial cell dynamics in vascular patterning in developing and developed vascular networks. We identified an important competition between blood flow and VEGF (an essential factor of blood vessel development) in the control of these dynamics in the developing networks. More interestingly, we also developed a new model for a known vascular disorder that is arteriovenous malformations, and demonstrated that some cellular behaviors are essential to their formation and their resolution which could lead the scientific community to the production of pro-resolution treatments for patients with identified arteriovenous malformations.