Manipulating Angiogenesis by Targeting Endothelial Metabolism: Hitting the Engine Rather than the Drivers-A New Perspective?

ABSTRACT

Excessive angiogenesis (i.e., the formation of new blood vessels) contributes to different pathologies, among them cancer and ocular disorders. Conversely, dysfunction of endothelial cells (ECs) contributes to cardiovascular complications, as is the case in diabetes. Inhibition of pathologic angiogenesis in blinding eye disease and cancer by targeting growth factors such as vascular endothelial growth factor has become an accepted therapeutic strategy. However, recent studies also unveiled the emerging importance of EC metabolism in controlling angiogenesis. In this overview, we will discuss recent insights in the metabolic regulation of angiogenesis, focusing on the best-characterized metabolic pathways, and highlight deregulation of EC metabolism in cancer and diabetes. We will give an outlook on how targeting EC metabolism can be used for blocking pathologic angiogenesis and for normalizing EC dysfunction.