Kininostatin as an antiangiogenic inhibitor: what we know and what we do not know.
High-molecular-weight kininogen (HK) is a plasma protein consisting of six domains (designated D1-D6). It was first characterized as a precursor of bradykinin, a bioactive peptide that regulates many cardiovascular processes. HK can bind to endothelial cells where it can be cleaved by plasma kallikrein to release bradykinin contained within domain 4. The remaining portion of the molecule, cleaved HK, is designated HKa. While bradykinin has been intensively studied, the physiological implication of the generation of HKa is not clear. HKa has recently been shown to inhibit the important steps required for angiogenesis such as proliferation and migration of endothelial cells. The antiangiogenic activity of HKa has further been demonstrated in animal models in which HKa inhibits neovascularization. Because domain 5 (D5) of HKa reproduces the antiangiogenic effect of HKa, D5 is named kininostatin for this novel function. In this review, we will briefly discuss the recent progress in the studies of the molecular mechanisms that mediate the antiangiogenic effect of HKa and D5.
Guo
Yan-Lin
YL
The Sol Sherry Thrombosis Research Center, Temple University School of Medicine, 3400 North Broad Street, Philadelphia, PA 19140, USA. yguo0002@astro.temple.edu
Wang
Shujie
S
Colman
Robert W
RW
D020533:Angiogenesis Inhibitors / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D019679:Kininogen, High-Molecular-Weight / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D009389:Neovascularization, Pathologic / Q000378:metabolism / Q000517:prevention & control*
D020533:Angiogenesis Inhibitors; D019679:Kininogen, High-Molecular-Weight