Increased plasma levels of plasminogen activator inhibitor-I and soluble vascular cell adhesion molecule after triacylglycerol infusion in man

Increased plasma plasminogen activator inhibitor-1 (PAI-1) has been implicated in the development of vascular disease. In type 2 diabetes mellitus high PAI-1 levels are associated with increased plasma concentrations of free fatty acids (FFA) and triacylglycerol indicating an association or a causal relationship. To answer that question, the effect of FFA/triacylglycerol on plasma PAI-1 was examined. Ten healthy male volunteers were studied for 6 h during infusion of triacylglycerol [1.5 ml/min]/heparin [ (0.2 IU/(kg.min)] (LIP; n= 10), saline only (SAL; n= 10), and saline/heparin (HEP; n=5). Plasma insulin concentrations were kept constant at similar to35 pmol/l by intravenous somatostatin-insulin infusions and there was no significant change in plasma glucose levels during any of the study protocols. LIP increased plasma triacylglycerol and FFA similar to3- (p<0.001) and similar to8-(p<0.000001) 1) fold, respectively, within 90 min. Baseline plasma PAI-1 measured by a bio-immunoassay was similar in HEP (11.4+/-2.8 ng/ml), SAL (16.6+/-3.6 ng/ml), and LIP studies (15.2+/- 3.4 ng/ml). Since studies were initiated in the morning, PAI-1 decreased (p<0.025) over time following its normal diurnal variation to 6.4+/-2.0 ng/ml and 4.0+/-2.4 ng/ml at 360 min in SAL and HEP, respectively. During LIP, however, PAI-1 increased to similar to2.6 fold higher levels than during SAL at 360 min (16.4+/-4.0 ng/ml, p<0.01). While tissue plasminogen activator (tPA) and adipsin, an adipocyte derived protease, were unaffected by LIP, changes in soluble vascular cell adhesion molecule-1 (sVCAM-1) were significantly correlated (p=0.02) with those seen for PAI-1. This suggests that hyperlipidemia independent of insulin and plasma glucose levels stimulates vascular tissue and in turn might induce an increase in plasma PAI-1. PAI-1 then could contribute to the development of atherothrombotic vascular disease.