Physiologic activities of the contact activation system.
Pubmed ID: 24759141
Pubmed Central ID: PMC4004333
Journal: Thrombosis research
Publication Date: May 1, 2014
MeSH Terms: Humans, Animals, Mice, Receptor, Bradykinin B2, Kininogen, High-Molecular-Weight, Factor XII, Kallikrein-Kinin System, Prekallikrein
Grants: R21 HL112666, R01 HL052779
Authors: Schmaier AH
Cite As: Schmaier AH. Physiologic activities of the contact activation system. Thromb Res 2014 May;133 Suppl 1(0 1):S41-4.
Studies:
Abstract
The plasma contact activation (CAS) and kallikrein/kinin (KKS) systems consist of 4 proteins: factor XII, prekallikrein, high molecular weight kininogen, and the bradykinin B2 receptor. Murine genetic deletion of factor XII (F12(-/-)), prekallikrein (Klkb1(-/-)), high molecular weight kininogen (Kgn1(-/-)) and the bradykinin B2 receptor (Bdkrb2(-/-)) yield animals protected from thrombosis. With possible exception of F12(-/-) and Kgn1(-/-) mice, the mechanism(s) for thrombosis protection is not reduced contact activation. Bdkrb2(-/-) mice are best characterized and they are protected from thrombosis through over expression of components of the renin angiotensin system (RAS) leading to elevated prostacyclin with vascular and platelet inhibition. Alternatively, prolylcarboxypeptidase, a PK activator and degrader of angiotensin II, when deficient in the mouse leads to a prothrombotic state. Its mechanism for increased thrombosis also is mediated in part by components of the RAS. These observations suggest that thrombosis in mice of the CAS and KKS are mediated in part through the RAS and independent of reduced contact activation.