Recombinant Human Kininostatin Protein

High molecular weight kininogen (HK) is a secreted plasma glycoprotein consisting of six domains (D1 through D6). It binds specifically to endothelial cells and serves as a substrate of plasma kallikrein which releases bradykinin from within D4 of HK. Bradykinin is an active peptide that regulates multiple vascular processes. The resulting cleaved HK, called HKa, is a disulfide-linked dimer containing a heavy chain (D1 to D3) and a light chain (D5 and D6). HKa differs from HK in conformation and possesses new functional properties. It is a potent angiogenesis inhibitor that strongly inhibits endothelial cell proliferation and migration. HKa also induces apoptosis of endothelial cells. D5 of HKa has been shown to be the active region primarily responsible for the HKa anti-angiogenic activity and has been named kininostatin. While both HK and HKa are plasma proteins that are present in circulation, it is not known if kininostatin (D5) can be released from HKa and exist in plasma (1 - 4).