Monocyte tissue factor response is decreased in patients with hyperlipidemia

Monocytes are potent regulators of blood coagulation through the expression of tissue factor (TF) on stimulation and of tissue factor pathway inhibito r (TFPI), a selective inhibitor of TF pathway. As hyperlipidemia can modify some monocyte functions, we compared the TF and TFPI expression by circula ting monocytes and the plasma TFPI levels between 65 healthy normolipemic c ontrols and 38 nontreated hyperlipemic patients. TF and TFPI relationships with plasma lipoproteins are also examined. TF and TFPI expression were eva luated in peripheral mononuclear cells after isolation from blood by densit y gradient centrifugation and after short culture with or without lipopolys accharide (LPS). TF and TFPI activity and antigen were measured in mononucl ear cell lysates using amidolytic assay and enzyme-linked immunosorbent ass ay, respectively. TFPI activity and antigen were measured in plasma using t he same methods. Plasma factor VII (FVII) activity and antigen were also de termined. LPS-stimulated monocyte TF activity and antigen were lower in hyp erlipidemic patients than in controls (0.0001<p<0.03). This decrease of mon ocyte TF expression in hyperlipidemic patients was not related to an increa se of monocyte TFPI. Monocyte TF activity was negatively correlated to athe rogenic fractions and positively correlated to protective fractions, specia lly after ex vivo LPS stimulation. Increased TFPI and FVII plasma levels we re found in hyperlipidemic patients compared to controls. These results ind icate an impairment of TF production by circulating monocytes from hyperlip idemic subjects, which is linked to the increase of atherogenic lipoprotein fractions. Further studies are required to elucidate the mechanism of this inhibition. (C) 1999 Elsevier Science Ltd. All rights reserved.