Study of the role of mitochondria during angiogenesis: can they provide a novel angiogenic target?

The essential function of the vasculature is to supply oxygen and nutrients to its surrounding tissues. In case any of those is lacking, new blood vessels are formed via angiogenesis to restore tissue equilibrium. Endothelial cells (EC), the major cell type of blood vessels, must be able to plastically adapt their metabolism to the funcitons they serve: survive and form a quiescent, tight interface between the blood and peripheral tissues in oxidative conditions, and actively form new vessels in anaerobic conditions. The role of mitochondrial metabolism during angiogenesis has been largely overlooked. I therefore will first characterize mitochondrial density and dynamics using a mouse model in which mitochondria of the EC are labeled with a green fluorescent protein. Second, a series of expression studies will be performed to investigate the contribution of different mitochondrial pathways in angiogenesis. I will investigate mitochondrial substrate fluxes and evaluate the effect of growth factor stimulation. Third, I will perform in vitro studies to define the role of several mitochondrial pathways in agiogenesis. Last, I will exploit this knowledge to create mice, that have EC deficiency for critical regulators of mitochondrial metabolism in order to explore their role during angiogenesis in vivo.

Keywords:Mitochondria, Metabolism, Endothelial cell, Angiogenesis

Disciplines:Biomaterials engineering, Biological system engineering, Biomechanical engineering, Other (bio)medical engineering, Environmental engineering and biotechnology, Industrial biotechnology, Other biotechnology, bio-engineering and biosystem engineering