is released by MMP2, MMP3, MMP7, MMP9, MMP12, MMP13 and MMP20 .
diminishes activation of the mitogen-activated protein kinases ERK-1 and ERK-2 in human dermal microvascular endothelial cells.
The effect of angiostatin
on vascular leakage and VEGF expression in rat retina.
and matrix metalloprotease expression following ischemic acute renal failure.
showed encouraging results in which its ability to shrink primary tumors and inhibit vascularization as well as metastatic colony development were confirmed both through in vitro and animal models.
The article concerned two new agents, endostatin and angiostatin
, developed by Harvard Professor judah Folkman, MD.
Some inhibitors are platelet and plasma-derived such as angiostatin
, endostatin, and platelet factor-4 (Daly et al.
Generation of biologically active angiostatin
kringle 1-3 by activated human neutrophils.
Two proteins, angiostatin
and endostatin, have been shown to possess anti-angiogenic activity.
MMP-9 can generate angiostatin
via an interaction with plasminogen, increase its affinity for collagen, interact with intercellular adhesion molecule-1, and be antiinflammatory by processing interleukin (IL)-1(3 from its precursor and by reducing IL-2 response.
For example, Judah Folkman first envisioned the idea of angiogenesis at the beginning of his career, more than forty years ago, yet neither endostatin nor angiostatin
, the potent antiangiogenesis drugs he developed, nor others in this category that have been developed by other researchers, had been approved by the Food and Drug Administration in mid-2004.
Although many synthetic and exogenous inhibitors of angiogenesis have been developed, the inhibitors that have received the most attention are the naturally derived endogenous proteins angiostatin