Relation between Plasminogen Activator Inhibitor-1 and Hepatic Enzyme Concentrations in Hyperlipidemic Patients

Summary

Plasminogen activator inhibitor type-1 (PAI-1) is a key determinant of the fibrinolytic capacity. Its activity correlates with most of the characteristic features of insulin resistance syndrome, i. e. obesity, high blood pressure and hyperlipidemia.

We measured plasma PAI-1 antigen levels in 131 asymptomatic men (aged 44.2 ± 11 years) who had been referred for hyperlipidemia. Those taking medication and those with a secondary hyperlipidemia were excluded.

We confirmed the correlation between PAI-1 levels and the following variables: body mass index, blood pressure, triglyceride concentration, and blood glucose and insulin levels before and after an oral glucose tolerance test. We also found a significant and independent correlation between PAI-1 and the concentration of the hepatic enzymes glutamyl transferase, alanine aminotransferase and aspartate aminotransferase.

Mild liver abnormalities (presumably steatosis) may thus be one of the factors accounting for high plasma PAI-1 levels in hyperlipidemic patients.

• References

• 1 Sprengers ED, Kluft C. Plasminogen activator inhibitors. Blood 1987; 69: 381-387
• 2 Oseroff A, Krishnamourti C, Hasset A, Tang D, Alving B. Plasminogen activator and plasminogen activator inhibitor activities in men with coronary artery disease. J Lab Clin Med 1989; 113: 88-93
• 3 Hamsten A, Faire U, Walldius G, Dahlen G, Szamosi A, Landou C, Blom-backe M, Wiman B. Plasminogen activator inhibitors in plasma: risk factor for recurrent myocardial infarction. Lancet 1987; 2: 3-8
• 4 Erickson LA, Fici GH, Lund JE, Boyle TP, Polites HG, Marotti KR. Development of venous occlusions in mice transgenic for the plasminogen activator inhibitor-1 gene. Nature 1990; 346: 74-76
• 5 Juhan-Vague I, Vague P, Alessi MC, Badier C, Valadier J, Aillaud MF, Atlan C. Relationships between plasma insulin triglyceride, Body Mass Index, and plasminogen activator inhibitor 1. Diabete et Metabolisme 1987; 13: 331-336
• 6 Crutchley DJ, McPhee GV, Terris MF, Canossa-Terris MA. Levels of three haemostatic factors in relation to serum lipids. Monocyte procoagulant activity, tissue plasminogen activator and type-1 plasminogen activator inhibitor Arteriosclerosis 1989; 9: 934-939
• 7 Metha J, Metha P, Lawson D, Saldeen T. Plasma tissue plasminogen activator inhibitor levels in coronary artery disease correlation with age and serum triglyceride concentrations. J Am Coll Cardiol 1987; 9: 263-268
• 8 Vague P, Juhan-Vague I, Chabert V, Alessi MC, Atlan C. Fat distribution and plasminogen activator inhibitor activity in nondiabetic obese women. Metabolism 1989; 38(9): 913-915
• 9 Landin K, Tengbom L, Smith U. Elevated fibrinogen and plasminogen activator inhibitor (PAI-1) in hypertension are related to metabolic risk factors for cardiovascular disease. Journal of Internal Medicine 1990; 22: 273-278
• 10 Cucuianu M, Zdrenghea D, Pop M, Opincaru A. Increased serum gamma-glutamyl transferase in hypertriglyceridemia: comparison with serum pseudocholine esterase. Clin Chim Acta 1976; 71: 419-427
• 11 Simpson HCR, Mann JL Meade TW, Chakrabarti R, Stirling Y, Woolf L. Hypertriglyceridemia and hypercoagulability. Lancet 1983; 1: 786-790
• 12 Assman G, Brewer Jr HB. Genetic (primary) forms of hyperlipidemia. Am J Cardiol 1991; 68: 13A-16A
• 13 Bruckert E, Ankri A, Jung M, Turpin G, De Gennes JL. Mild liver abnormalities are associated with elevated plasma factor VII and protein C in hypertriglyceridemic patients. Eur J Med 1993; 8: 461-465
• 14 Fruchart JC, Beucler I, Blaton V, Canal J, Douste-Blazy L, Gambert P, Ka-terman R, Legrand A, Polonowski J, Steinmetz J, Thouvenot JP. Methode selectionnee pour le dosage du cholesterol des lipoproteines non precipi-tables par le phospho-tungstate de sodium en presence de chlorure de magnesium. Inf Scient Biol 1982; 8: 69-72
• 15 Mussoni L, Mannucci L, Sirtori M, Camera M, Madema P, Sironi L, Tre-moli E. Hypertriglyceridemia and regulation of fibrinolytic activity. Arteriosclerosis and Thrombosis 1992; 12: 19-27
• 16 Friedewald WT, Levy RI, Fredrickson DS. Estimation of the concentration of low-density lipoprotein cholesterol in plasma without the use of the preparative ultracentrifuge. Clin Chem 1972; 18: 499-502
• 17 Reaven GM. Banting Lecture 1988. Role of insulin resistance in human disease. Diabetes 1988; 37: 1595-1607
• 18 Bruckert E, Dairou F, De Gennes JL. Complications cardiovasculaires de rhypertriglyceridemie endogene mineure. Arch Mai Coeur 1987; 11: 1587-92
• 19 Aberg H, Lithell H, Selinus I, Hedstrand J. Serum triglycerides as a risk factor for myocardial infarction but not angina pectoris. Results from a 10 years follow up of Uppsala primary preventive study. Atherosclerosis 1985; 54: 89-97
• 20 Grant PJ, Kruithof EKO, Felley CP, Felber JP, Bachmann F. Short-term infusions of insulin, triacylglycerol and glucose do not cause acute inreases in plasminogen activator inhibitor 1 concentrations in man. Clin Sci 1990; 79: 513-516
• 21 Juhan-Vague I, Vague P. Hypofibrinolysis and insulin resistance. Diab Metab 1991; 17(Suppl 2): 96-100
• 22 Latron Y, Chautan M, Anfosso F, Alessi G, Nalbone G, Lafont H, Juhan-Vagu I. Stimulating effect of oxidized low density lipoprotein on plasminogen activator inhibitor-1 synthesis by endothelial cells. Arteriosclerosis and Thrombosis 1991; 11: 1821-1829
• 23 Stiko-Rahm A, Wiman B, Hamsten A, Nilsson J. Secretion of plasminogen activator inhibitor-1 from cultured human umbilical vein endothelial cells is induced by very low density lipoprotein. Arteriosclerosis 1990; 10: 1067-1073
• 24 Asplund-Carlson A, Hamsten A, Wiman B, Carlson LA. Relationship between plasma plasminogen activator inhibitor-1 activity and VLDL triglyceride concentration, insulin levels and insulin sensitivity: studies in randomly selected normo- and hypertriglyceridaemic men. Diabetologia 1993; 36: 817-825
• 25 Tran-Thang C, Fasel-Felley J, Pralong G, Hogfsetter JR, Bachmann F, Kruithof EKO. Plasminogen activator and plasminogen activator inhibitors in liver deficiencies caused by chronic alcoholism or infectious hepatitis. Thromb Haemost 1989; 62 (02) 651-653
• 26 iest G, Henny J, Schiele F. References en biologie clinique. Elsevier editions scientifiques 1990; 275-293
• 27 Braillon A, Capron JP. Foie et obesite. Gastroenterol Clin Biol 1983; 7: 627-34