Physiologic activities of the contact activation system.
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.
Division of Hematology and Oncology, Case Western Reserve University, University Hospitals Case Medical Center, Cleveland, OH 44106, United States. Electronic address: Schmaier@case.edu.
Alvin H
AH
Schmaier
D000818:Animals; D005174:Factor XII / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D016234:Kallikrein-Kinin System; D019679:Kininogen, High-Molecular-Weight / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D011288:Prekallikrein / Q000235:genetics / Q000378:metabolism*; D043782:Receptor, Bradykinin B2 / Q000235:genetics / Q000378:metabolism*
D019679:Kininogen, High-Molecular-Weight; D043782:Receptor, Bradykinin B2; D005174:Factor XII; D011288:Prekallikrein
Angiotensin receptor 2; Bradykinin B2 receptor; Contact activation; Factor XII; High molecular weight kininogen; Kallikrein/kinin system; Mas receptor; Prekallikrein; Prolycarboxypeptidase; Renin angiotensin system