Increased plasma levels of plasminogen activator inhibitor-1 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 approximately 35 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 approximately 3- (p < 0.001) and approximately 8- (p < 0.000001) 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 approximately 2.6 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.
Krebs
Michael
M
Department of Vascular Biology and Thrombosis Research, University of Vienna, Schwarzspanierstrasse 17, A-1090 Vienna, Austria.
Geiger
Margarethe
M
Polak
Kaija
K
Vales
Anja
A
Schmetterer
Leopold
L
Wagner
Oswald F
OF
Waldhäusl
Werner
W
Binder
Bernd R
BR
Roden
Michael
M
D000328:Adult; D001786:Blood Glucose; D011416:Complement Factor D; D005227:Fatty Acids / Q000097:blood; D006493:Heparin / Q000008:administration & dosage / Q000494:pharmacology; D006801:Humans; D006949:Hyperlipidemias / Q000097:blood; D007263:Infusions, Parenteral; D007328:Insulin / Q000097:blood; D007700:Kinetics; D008297:Male; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood*; D011446:Prospective Studies; D012697:Serine Endopeptidases / Q000097:blood; D012995:Solubility; D010959:Tissue Plasminogen Activator / Q000097:blood; D014280:Triglycerides / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D019010:Vascular Cell Adhesion Molecule-1 / Q000097:blood*
D001786:Blood Glucose; D005227:Fatty Acids; D007328:Insulin; D017395:Plasminogen Activator Inhibitor 1; D014280:Triglycerides; D019010:Vascular Cell Adhesion Molecule-1; D006493:Heparin; D012697:Serine Endopeptidases; C493488:CFD protein, human; D011416:Complement Factor D; D010959:Tissue Plasminogen Activator