Response of plasma tissue factor pathway inhibitor to diet-induced hypercholesterolemia in crab-eating monkeys

Abstract

Tissue factor pathway inhibitor (TFPI), a protease inhibitor associated with lipoproteins in plasma and endothelial cells, can inhibit the initial reactions of the tissue factor-mediated coagulation pathway. A positive relationship between TFPI and cholesterol has been demonstrated in human plasma. To investigate this relation in more detail, in the present study we measured TFPI in the plasma of monkeys on a high-cholesterol diet. After diet treatment, cholesterol levels and TFPI activity were increased 3- and 1.5-fold, respectively. Three forms of TFPI, low-density lipoprotein (LDL)/very-low-density lipoprotein (VLDL)-associated TFPI, high-density lipoprotein (HDL)-associated TFPI, and free TFPI, were measured after gel filtration of plasma. In hypercholesterolemic monkeys, levels of TFPI activity and antigen in the LDL/VLDL fraction were increased to about three times those of normal monkeys. Changes in HDL-associated TFPI and free TFPI were not significant compared with the change in LDL/VLDL-associated TFPI. After the monkeys received heparin infusions TFPI was increased about fivefold, but there was no significant difference in these increases between normal and hypercholesterolemic monkeys. The increase in TFPI after heparin infusion is discussed in terms of the relationship between lipoprotein-associated TFPI in plasma and endothelial cell-associated TFPI.