Human angiostatin is a naturally occurring protein. Human angiostatin is an endogenous angiogenesis inhibitor. Angiogenesis inhibitor is responsible for blocking growth of new blood vessels in the body. Angiostatin is a fragment of a larger protein called plasmin. This is a 38k Da fragment of plasmin. Plasmin is again a fragment of plasminogen. Auto proteolytic cleavage of plasminogen leads to generation of angiostatin. The cleavage of plasminogen is aided by elastase, metalloproteinases, prostate- specific antigen, and 24KD endopeptidase, and result in production of angiostatin. The plasminogen constitutes of kringles 1-4.This 38 KD fragment is responsible for inhibition of blood vessel formation in animal tumour models and in vitro endothelial cell models. There has been yet no evidence on testing of human angiostatin in vitro on intact human tissues for determination of its ability to inhibit initiation or promotion of angiogenic response.

Angiostatin binds to various proteins especially angiomotin, ATP synthase on endothelial cell surface, annexin II, integrins and CD26. Further smaller fragments of angiostatin bind to various other proteins. The mechanism of action of angiostatin at present involves various uncertainties and is still under study. But it does have an involvement in inhibition of endothelial cell migration, propagation and induction of apoptosis. The in vivo enzymatic mechanism of angiostatin generation is not known. Recent studies have shown serine proteinase to be responsible for cleavage of plasminogen and generation of angiostatin. Tumour growth can be dramatically impaired if angiogenesis is prevented.