Tissue-factor pathway inhibitor and lipoproteins. Evidence for association with and regulation by LDL in human plasma

J B Hansen, N E Huseby, P M Sandset, B Svensson, V Lyngmo, A Nordøy
1994 Arteriosclerosis and Thrombosis A Journal of Vascular Biology  
Tissue-factor pathway inhibitor (TFPI) is a potent inhibitor of extrinsic coagulation, which is mainly associated with lipoproteins in circulating blood. Gel filtration of human plasma confirmed the presence of three peaks in which approximately 10%, 70%, and 20% of total TFPI activity was retained. Precipitation of very-low-density lipoproteins and low-density lipoproteins (LDLs) in plasma by polyethylene glycol almost completely abolished peaks I and II. LDL isolated by ultracentrifugation
more » ... ealed two peaks of TFPI after gel filtration that coeluted with peaks I and II, respectively, from gel filtration of total plasma. TFPI activity in peaks I and II was also precipitated by anti-apolipoprotein B antibodies. Fourteen patients with familial hypercholesterolemia had higher plasma TFPI activity than did age-and sexmatched normolipemic control subjects (1.45±0.27 U/mL versus 0.80±0.09 U/mL, i><.001). Plasma TFPI was correlated with LDL cholesterol (r=.73, Z'<.001) and apolipoprotein B (r=.69, P<.001). No association was found with high-density lipoprotein cholesterol or apolipoprotein A-I. In a doubleblind, placebo-controlled trial among the familial hypercholesterolemia patients, lovastatin alone or in combination with fish oil concentrate lowered plasma TFPI in parallel with LDL cholesterol. Gel filtration of plasma from these patients demonstrated a specific drop in apolipoprotein B-TFPI complexes, whereas TFPI not associated with lipoproteins was unchanged. This study demonstrated that plasma TFPI was associated with and regulated by LDL in plasma from healthy subjects and patients with familial hypercholesterolemia. (Arterioscler Thromb. 1994;14:223-229.) Key Words • lovastatin • HMG-CoA reductase inhibitors • familial hypercholesterolemia • tissue-factor pathway inhibitor • lipoproteins
doi:10.1161/01.atv.14.2.223 fatcat:uxexty7h7baxffyhombdhmwypa