Forces that control endothelial adhesion in angiogenesis

Angiogenesis, the formation of new blood vessels from preexisting ones, is regulated by collective migration of endothelial cells, by dynamic remodeling of their cell – cell and cell – extracellular matrix adhesions. During angiogenesis, the mechanical forces subjected to the endothelial layer change, including matrix rigidity, hemodynamic forces and actin cytoskeletal contractility. The endothelial adhesions can sense and transmit these forces into biochemical signaling, resulting in changes in gene expression, adhesion, migration, proliferation and angiogenesis. In this thesis, we examined how different endothelial signaling events regulate sprouting angiogenesis via modulation of cell – cell and cell- extracellular matrix adhesions. Using in vitro and in vivo angiogenic sprouting models we describe how endothelial functions are modulated by internal processes such as cholesterol biosynthesis and cytoskeletal-mechanotransduction, but also by external stimuli, like extracellular matrix stiffening and hemodynamic forces, and the implications that these have for angiogenic processes. Overall, this thesis contributes to a better understanding of the endothelial adhesion mechanotransductory processes during angiogenesis.