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(Arteriosclerosis, Thrombosis, and Vascular Biology. 1995;15:879-885.)
© 1995 American Heart Association, Inc.

Articles

Effect of Cholesterol Lowering on Intravascular Pools of TFPI and Its Anticoagulant Potential in Type II Hyperlipoproteinemia

John-Bjarne Hansen; Kirsten Raanaas Huseby; Nils-Erik Huseby; Per Morten Sandset; Tor-Arne Hanssen; Arne Nordøy

From the Department of Medicine, Institute of Clinical Medicine (J.-B.H., K.R.H., T.-A.H., A.N.), and Department of Clinical Chemistry, Institute of Medical Biology (N.-E.H.), University of Tromsø, and the Department of Medicine, Ullevål University Hospital, Oslo (P.M.S.), Norway.

Correspondence to John-Bjarne Hansen, Institute of Clinical Medicine, Department of Medicine, University of Tromsø, N-9037 Tromsø, Norway.

Abstract Tissue factor pathway inhibitor (TFPI) inhibits the extrinsic coagulation system. A major pool of TFPI is associated with the vascular endothelium and can be mobilized into the circulation by heparin. In circulating blood, TFPI is mainly associated with LDL (80%), whereas 10% to 20% is carrier free. In this study, heparin administration caused a 2.2-fold and a 7.5-fold increase in TFPI activity and TFPI antigen, respectively, in 25 patients with phenotypes IIa and IIb hyperbetalipoproteinemia. Because the antigen determination of TFPI almost exclusively measures carrier-free TFPI, more than 90% of the heparin-induced increase in TFPI activity was caused by mobilization of carrier-free TFPI from the vascular endothelium. Therapeutic lowering of total cholesterol (a decrease of 31.1±11.6%, P<.001) by 40 mg/d lovastatin in 17 patients with hyperbetalipoproteinemia was accompanied by a parallel decrease in TFPI activity (of 27.7±24.2%, P<.001) because of a reduction in LDL-TFPI complexes. However, drug intervention did not affect carrier-free TFPI or the magnitude of the vascular pool of TFPI that could be mobilized into the circulation by heparin. Moreover, this reduction of LDL-TFPI complexes did not reduce the anticoagulant potency of TFPI in plasma or of the vascular endothelial pool. The results of this study may imply that the anticoagulant potency of TFPI is associated with its carrier-free form in plasma or on the endothelium and that downregulation of LDL affects neither the size nor the anticoagulant potency of the endothelial pool of TFPI.

Key Words: lipoproteins • anticoagulant potential • tissue factor pathway inhibitor • hyperlipoproteinemia • lovastatin

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