Human Plasma Kallikrein-Kinin System: Physiological and Biochemical Parameters

Author(s): J. W. Bryant, Z. Shariat-Madar

Journal Name: Cardiovascular & Hematological Agents in Medicinal Chemistry
Formerly Current Medicinal Chemistry - Cardiovascular & Hematological Agents

Volume 7 , Issue 3 , 2009

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The plasma kallikrein-kinin system (KKS) plays a critical role in human physiology. The KKS encompasses coagulation factor XII (FXII), the complex of prekallikrein (PK) and high molecular weight kininogen (HK). The conversion of plasma prekallikrein to kallikrein by the activated FXII and in response to numerous different stimuli leads to the generation of bradykinin (BK) and activated HK (HKa, an antiangiogenic peptide). BK is a proinflammatory peptide, a pain mediator and potent vasodilator, leading to robust accumulation of fluid in the interstitium. Systemic production of BK, HKa with the interplay between BK bound-BK receptors and the soluble form of HKa are key to angiogenesis and hemodynamics. KKS has been implicated in the pathogenesis of inflammation, hypertension, endotoxemia, and coagulopathy. In all these cases increased BK levels is the hallmark. In some cases, the persistent production of BK due to the deficiency of the blood protein C1-inhibitor, which controls FXII, is detrimental to the survival of the patients with hereditary angioedema (HAE). In others, the inability of angiotensin converting enzyme (ACE) to degrade BK leads to elevated BK levels and edema in patients on ACE inhibitors. Thus, the mechanisms that interfere with BK liberation or degradation would lead to blood pressure dysfunction. In contrast, anti-kallikrein treatment could have adverse effects in hemodynamic changes induced by vasoconstrictor agents. Genetic models of kallikrein deficiency are needed to evaluate the quantitative role of kallikrein and to validate whether strategies designed to activate or inhibit kallikrein may be important for regulating whole-body BK sensitivity.

Keywords: The plasma-kallikrein-kinin system (KKS), prolylcarboxypeptidase, prekallikrein, kallikrein inhibitors, high molecular weight kininogen, inflammation, sepsis

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Article Details

Year: 2009
Page: [234 - 250]
Pages: 17
DOI: 10.2174/187152509789105444
Price: $65

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