Summary

Atherosclerosis is a dynamic disease involving lipid metabolism,inflammation and thrombosis.A key factor in thrombosis is tissuefactor, a small transmembrane glycoprotein. Tissue factorbinds FactorVIIa, and this complex converts Factor X to FactorXa, leading to thrombin generation and fibrin formation. Inhibitionof this pathway is by tissue factor pathway inhibitor(TFPI).Tissue factor is found sequestered within atheroscleroticplaques, and plaque rupture allows tissue factor exposure to thecirculation, leading to formation of a thrombus.Tissue factor isalso associated with membrane microparticles in the circulation,most likely released from monocytes activated by an inflammatoryevent.We hypothesize that consumption of a typicalwestern diet that is moderate in fat content leads to elevated levelsof circulating tissue factor that may act as a marker of a prothrombotic state. Healthy volunteers, aged 18–55, consumed amoderate (40%) fat meal, with blood taken before and 3.5 and 6h after the meal.Plasma was isolated and assayed for plasma triglycerides,tissue factor, thrombin antithrombin (TAT) complexes,TFPI and TNFa . The levels of circulating tissue factor increased56% (from 78 pg/ml to120 pg/ml) 3.5 h after the meal.Levels decreased,but had not returned to baseline 6 h postprandially.No significant differences in TAT, TFPI and TNFa levelswere observed postprandially. These results demonstrate increasedtissue factor levels in individuals who consumed a moderatefat diet.This suggests that the typical western diet may playa larger role in cardiovascular disease than merely altering lipidprofiles.