RRML - Anticoagulant mechanisms are modulated by vascular endothelial cells

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Dr. Adrian Man

Nr. 18(3)/2010

Anticoagulant mechanisms are modulated by vascular endothelial cells

Ioana Brudaşcă, Mircea Cucuianu

Abstract:

The function of the main anticoagulant mechanisms (antithrombin and protein C system) depends not only on the available amounts of these proteins, but also on the modulation of their activity by components located on vascular endothelial cells’ membrane. Antithrombin is activated by the heparansulphate expressed on the endothelial cells, and impaired interaction between heparansulphate and the antithrombin molecule may occur in relation to an immune aggression (such as in heparin-induced thrombocytopenia) and/or to the enzymatic cleavage exerted by heparanase on heparansulphate. Heparanase has a prothrombotic effect through the downregulation of antithrombin anticoagulation and also through the induction of tissue factor and the dissociation of the tissue factor pathway inhibitor (TFPI) from the endothelial cells membrane. The protein C activation complex is represented by thrombin bound to endothelial thrombomodulin, which would act on protein C bound to a specific endothelial receptor, EPCR. Proinflammatory cytokines would exert deleterious effects on thrombomodulin and on EPCR, thereby impairing PC activation. The protein C bound to EPCR was reported to exert anti-inflammatory, cytoprotective and anti-apoptotic effects. Actually, by signaling through the same protease activated receptor (PAR-1), thrombin would elicit a proinflammatory response, while in the presence of either activated protein C (APC) or protein C bound to its specific endothelial receptor (EPCR), the signal transduced by this thrombin prototypic receptor would produce anti-inflammatory effects. The assessment of the circulating soluble forms of EPCR and thrombomodulin, as well as TFPI (dissociated from the cellular membrane by heparanase) could provide markers of endothelial damage.

Keywords: antithrombin,heparanase,protein C,EPCR,thrombomodulin,PAR-1,TFPI,endothelial damage

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Brudaşcă I, Cucuianu M. Anticoagulant mechanisms are modulated by vascular endothelial cells. Rev Romana Med Lab. 2010;18(3):7-14