Inhibition of angiogenesis: a new function for angiotensinogen and des(angiotensin I)angiotensinogen

Angiotensinogen (AGT) can be schematically considered to consist of a combination of an angiotensin I (Ang I) function, located at the N-terminal end, and the presence of a serpin (serine protease inhibitor) structure at the opposite end. des(Ang I)AGT, which accounts for more than 97% of the molecule, apparently has no function. Several serpins (antithrombin, maspin, pigment epithelial-derived factor, and kallistatin) have been recently shown to exert an antiangiogenic activity, suggesting a common mechanism of endothelial cell proliferation and migration. AGT and its renin-cleaved product, des(Ang I)AGT, are also angiogenesis inhibitors, both in vitro and in vivo at concentrations within the range of those observed in plasma. This property most likely results from the structure analogy of AGT with serpins. The pathologic relevance of this new function is still not known, but AGT produced by glial cells may play a role in the stabilization of the blood-brain barrier. These new data must be considered in light of the overall action of the renin-angiotensin system in angiogenesis.