Increased plasma levels of plasminogen activator inhibitor-1 and soluble vascular cell adhesion molecule after triacylglycerol infusion in man.

Abstract

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.

• Authors: Michael Krebs, Margarethe Geiger, Kaija Polak, Anja Vales, Leopold Schmetterer, Oswald F Wagner, Werner Waldhäusl, Bernd R Binder, Michael Roden
• Journal: Thrombosis and haemostasis (Thromb Haemost) Vol. 90 Issue 3 Pg. 422-8 (Sep 2003) ISSN: 0340-6245 [Print] Germany
• PMID: 12958610 (Publication Type: Clinical Trial, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Blood Glucose
• Fatty Acids
• Insulin
• Plasminogen Activator Inhibitor 1
• Triglycerides
• Vascular Cell Adhesion Molecule-1
• Heparin
• Serine Endopeptidases
• CFD protein, human
• Complement Factor D
• Tissue Plasminogen Activator

Topics

• Adult
• Blood Glucose
• Complement Factor D
• Fatty Acids (blood)
• Heparin (administration & dosage, pharmacology)
• Humans
• Hyperlipidemias (blood)
• Infusions, Parenteral
• Insulin (blood)
• Kinetics
• Male
• Plasminogen Activator Inhibitor 1 (blood)
• Prospective Studies
• Serine Endopeptidases (blood)
• Solubility
• Tissue Plasminogen Activator (blood)
• Triglycerides (administration & dosage, blood, pharmacology)
• Vascular Cell Adhesion Molecule-1 (blood)