Delta-like 4 and vasohibin 1: Two endothelium-produced negative regulators of angiogenesis with distinctive roles

Angiogenesis is regulated by the local balance between angiogenesis stimulators and inhibitors. A number of endogenous angiogenesis inhibitors have been found in the body. The origin of these inhibitors is mostly extrinsic to the vasculature. Recently however, endothelial cells themselves have been found to produce angiogenesis inhibitors including delta-like 4 and vasohibin 1. These intrinsic factors are thought to regulate angiogenesis by an autoregulatory or negative-feedback mechanism. This review focuses on such negative regulators of angiogenesis produced by endothelial cells.