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

Thromb Haemost. 2003 Sep;90(3):422-8. doi: 10.1160/TH03-07-0457.


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.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Blood Glucose
  • Complement Factor D
  • Fatty Acids / blood
  • Heparin / administration & dosage
  • Heparin / 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
  • Triglycerides / blood
  • Triglycerides / pharmacology*
  • Vascular Cell Adhesion Molecule-1 / blood*


  • 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