Endogenous inhibitors of angiogenesis: A historical review

Under physiological conditions, angiogenesis is regulated by the local balance between endogenous stimulators and inhibitors of this process. In pathological states such as chronic inflammation and tumor growth, there is an imbalance between endogenous stimulator and inhibitor levels, leading to an “angiogenic switch”. Various inhibitors of angiogenesis, including angiostatin, endostatin and thrombospondins, are found in the body. It is uncertain why the body possesses so many inhibitors, and also how these inhibitors interact to overcome the effects of angiogenesis stimulators. This review summarizes the present knowledge about endogenous inhibitors of angiogenesis.