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Thromb Haemost 2003; 90(03): 422-428
DOI: 10.1160/TH03-07-0457
Blood Coagulation, Fibrinolysis and Cellular Haemostasis
Schattauer GmbH

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

Michael Krebs
1   Departments of Vascular Biology and Thrombosis Research, Division of Endocrinology and Metabolism, University of Vienna Medical School, Vienna, Austria
5   Departments of Internal Medicine III, Division of Endocrinology and Metabolism, University of Vienna Medical School, Vienna, Austria
,
Margarethe Geiger
1   Departments of Vascular Biology and Thrombosis Research, Division of Endocrinology and Metabolism, University of Vienna Medical School, Vienna, Austria
,
Kaija Polak
2   Departments of Clinical Pharmacology, Division of Endocrinology and Metabolism, University of Vienna Medical School, Vienna, Austria
,
Anja Vales
1   Departments of Vascular Biology and Thrombosis Research, Division of Endocrinology and Metabolism, University of Vienna Medical School, Vienna, Austria
,
Leopold Schmetterer
2   Departments of Clinical Pharmacology, Division of Endocrinology and Metabolism, University of Vienna Medical School, Vienna, Austria
3   Departments of Medical Physics, Division of Endocrinology and Metabolism, University of Vienna Medical School, Vienna, Austria
,
Oswald F. Wagner
4   Departments of Medical, Division of Endocrinology and Metabolism, University of Vienna Medical School, Vienna, Austria
,
Werner Waldhäusl
5   Departments of Internal Medicine III, Division of Endocrinology and Metabolism, University of Vienna Medical School, Vienna, Austria
,
Bernd R. Binder
1   Departments of Vascular Biology and Thrombosis Research, Division of Endocrinology and Metabolism, University of Vienna Medical School, Vienna, Austria
,
Michael Roden
5   Departments of Internal Medicine III, Division of Endocrinology and Metabolism, University of Vienna Medical School, Vienna, Austria
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Publikationsverlauf

Received 10. Januar 2002

Accepted after resubmission 28. Mai 2003

Publikationsdatum:
05. Dezember 2017 (online)

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Summary

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 ~35 pmol/l by intravenous soma-tostatin-insulin infusions and there was no significant change in plasma glucose levels during any of the study protocols. LIP increased plasma triacylglycerol and FFA ~3- (p<0.001) and ~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 ~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.

Keywords

Fibrinolysis - PAI-1 - VCAM-1 - adhesion molecules - vascular disease - insulin resistance - free fatty acids
 

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