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• W2102727554 endingPage "465" @default.
• W2102727554 startingPage "461" @default.
• W2102727554 abstract "β2-glycoprotein-I (β2GPI) is a phospholipid-binding plasma protein that consists of five homologous domains. Domain V is distinguished from others by bearing a positively charged lysine cluster and hydrophobic extra C-terminal loop. β2GPI has been known as a natural anticoagulant regulator. β2GPI exerts anticoagulant activity by inhibition of phospholipid-dependent coagulation reactions such as prothrombinase, tenase, and factor XII activation. It also binds factor XI and inhibits its activation. On the other hand, β2GPI inhibits anticoagulant activity of activated protein C. According to the data from knockout mice, β2GPI may contribute to thrombin generation in vivo. Phospholipid-bound β2GPI is one of the major target antigens for antiphospholipid antibodies present in patients with antiphospholipid syndrome (APS). Binding of pathogenic anti-β2GPI antibodies increases the affinity of β2GPI to the cell surface and disrupts the coagulation/fibrinolysis balance on the cell surface. These pathogenic antibodies activate endothelial cells via signal transduction events in the presence of β2GPI. Impaired fibrinolysis has been reported in patients with APS. Using a newly developed chromogenic assay, we demonstrated lower activity of intrinsic fibrinolysis in euglobulin fractions from APS patients. Addition of monoclonal anti-β2GPI antibodies with β2GPI also decreased fibrinolytic activity in this assay system. β2GPI is proteolytically cleaved by plasmin in domain V (nicked β2GPI) and becomes unable to bind to phospholipids, reducing antigenicity against antiphospholipid antibodies. This cleavage occurs in patients with increased fibrinolysis turnover. Nicked β2GPI binds to plasminogen and suppresses plasmin generation in the presence of fibrin, plasminogen, and tissue plasminogen activator (tPA). Thus, nicked β2GPI plays a role in the extrinsic fibrinolysis via a negative feedback pathway loop." @default.
• W2102727554 created "2016-06-24" @default.
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• W2102727554 date "2004-01-01" @default.
• W2102727554 modified "2023-09-27" @default.
• W2102727554 title "β2-glycoprotein I, anti-β2-glycoprotein I, and fibrinolysis" @default.
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• W2102727554 doi "https://doi.org/10.1016/j.thromres.2004.07.013" @default.
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