Progress in the understanding of the protein C anticoagulant pathway.

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Abstract

A natural anticoagulant pathway denoted the protein C system provides specific and efficient control of blood coagulation. Protein C is the key component of the system and circulates in the blood as a zymogen to an anticoagulant serine protease.Activation of protein C is achieved on the surface of endothelial cells by thrombin bound to the membrane protein thrombomodulin. The endothelial protein C receptor stimulates the activation of protein C on the endothelium. Activated protein C (APC) modulates blood coagulation by cleaving a limited number of peptide bonds in factor VIIIa (FVIIIa) and factor Va (FVa), cofactors in the activation of factor X and prothrombin, respectively.Vitamin K-dependent protein S stimulates the APC-mediated regulation of coagulation. Not only is protein S involved in the degradation of FVIIIa, but so is FV, which in recent years has been found to be a Janus-faced protein with both procoagulant and anticoagulant potentials.A number of genetic defects affecting the anticoagulant function of the protein C system, eg,APC resistance (Arg506Gln or FV Leiden) and deficiencies of protein C and protein S constitute major risk factors of venous thrombosis.The protein C system also has anti-inflammatory and antiapoptotic potentials,the molecular mechanisms of which are beginning to be unraveled.APC has emerged in recent years as a useful therapeutic compound in the treatment of severe septic shock.The beneficial effect of APC is believed be due to both its anticoagulant and its anti-inflammatory properties.

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  • Medicinal Chemistry
Original languageEnglish
Pages (from-to)109-116
JournalInternational Journal of Hematology
Volume79
Issue number2
Publication statusPublished - 2004
Publication categoryResearch
Peer-reviewedYes