Daytime Fluctuations of Plasminogen Activator Inhibitor 1 (PAI-1) in Populations with High PAI-1 Levels

Summary

The mechanism underlying diurnal variations in PAI-1 as well as the cellular origin of PAI-1 in subjects with high PAI-1 levels are unknown. We evaluated diurnal changes (8:00 am vs 4:00 pm) in PAI-1 (functional and immunological assays), t-PA Ag and t-PA/PAI-1 complex levels in controls and subjects with high PAI-1 levels. Three test groups were recruited among obese hyperinsulinmic subjects, emergency care unit patients with inflammatory syndrome or infection and pregnant women.

The classical afternoon decrease of PAI-1 level was observed in controls and obese subjects but its amplitude was greater in the latter. The decrease in t-PA Ag and t-PA/PAI-1 complex levels was the same in controls and in obese. As, in previous studies, elevated PAI-1 levels have been correlated with insulin resistance and a decrease in insulin sensibility has been described in the early morning, it is proposed that this “dawn phenomenon” could be implicated in the circadian variations of PAI-1 in controls and could be amplified in obese subjects. Great variability in PAI-1, t-PA Ag or t-PA/PAI-1 complex levels was observed in patients with acute inflammatory syndrome or infection for whom classical biorhythms are suppressed. No diurnal changes in PAI-1 and other fibrinolytic parameters were observed in patients with inflammatory syndrome or in pregnant women suggesting that other sources and/or other regulatory mechanisms of PAI-1 production are involved.

• References

• 1 Fearnley GR, Balmforth G, Fearnley E. Evidence of a diurnal fibrinolytic rhythm with a simple method of measuring fibrinolysis. Clin Sei 1957; 16: 645-650
• 2 Rosing DR, Brakman P, Redwood DR, Goldstein RE, Beiser GD, Astrup T, Epstein E. Blood fibrinolytic activity in man. Diurnal variation and the response to varying intensities of exercise. Circulation Res 1970; 27: 171-184
• 3 Cepelak V, Bareal R, Cepelakova H, Mayer O. Circadian rhythm of fibrinolysis. In: Progress in Chemical Fibrinolysis and Thrombosis Vol. III. Davidson JF, Rowan RM, Samama MM, Desnoyers PC. (eds). Raven Press; New York: 1978. pp 571-578
• 4 Kluft C, Verheijen JH, Rijken DC, Chang GTG, Jie AFH, Onkelinx C. Diurnal fluctuations in the activity in blood of the fast-acting t-PA inhibitor. In: Progress in Fibrinolysis Vol VII. Davidson JF, Donati MB, Coccheri S. (eds). Churchill Livingstone; Edinburgh: 1985. pp 117-119
• 5 Andreotti F, Davies GJ, Hackett D, Khan MI, de Bart A, Dooije-waard G, Maseri A, Kluft C. Circadian variation of fibrinolytic factors in normal human plasma. Fibrinolysis 1988; 2 (Suppl) (02) 90-92
• 6 Grimaudo V, Hauert J, Bachmann F, Kruithof EKO. Diurnal variation of the fibrinolytic system. Thromb Haemostas 1988; 59: 495-499
• 7 Huber K, Rose D, Resch I, Schuster E, Glogar DH, Kaindl F, Binder BR. Circadian fluctuations of plasminogen activator inhibitor and tissue plasminogen activator levels in plasma of patients with unstable coronary artery disease and acute myocardial infarction. Thromb Haemostas 1988; 60: 372-376
• 8 Kluft C, Jie AFH, Rijken DC, Verheijen JH. Daytime fluctuations in blood of tissue-type plasminogen activator (t-PA) and its fast acting inhibitor PAI-1. Thromb Haemostas 1988; 59: 329-332
• 9 Angleton P, Chandler WL, Schmer G. Diurnal variation of tissue-type plasminogen activator and its rapid inhibitor (PAI-1). Circulation 1989; 79: 101-106
• 10 Chandler WL, Mornin D, Whitten RO, Angleton P, Farin FM, Fritsche TR, Veith RC, Stratton JR. Insulin, cortisol and catecholamines do not regulate circadian variations in fibrinolytic activity. Thromb Res 1990; 58: 1-12
• 11 Hamsten A, de Faire M, Walldius G, Dahlen G, Szamosi A, Landau C, Blombäck M, Wiman B. Plasminogen activator inhibitor in plasma: risk factor for recurrent myocardial infarction. Lancet 1987; 2: 3-9
• 12 Muller JE, Ludmer PL, Wilich SN, Tofler GH, Aylmer G, Klangos I, Stone PH. Circadian variation in the frequency of sudden cardiac death. Circulation 1987; 75: 131-138
• 13 Marshall J. Diurnal variation in occurrences of strokes. Stroke 1977; 88: 230-231
• 14 Andreotti F, Davies GJ, Hackett DR, Khan MI, de Bart ACW, Aber VR, Maseri A, Kluft C. Major circadian fluctuations in fibrinolytic factors and possible relevance to time of onset of myocardial infarction, sudden cardiac death and stroke. Am J Cardiol 1988; 62: 635-637
• 15 Hamsten A, Wiman B, de Faire U, Blomback M. Increased plasma level of a rapid inhibitor of tissue plasminogen activator in young survivors of myocardial infarction. N Engl J Med 1985; 313: 1557-1563
• 16 Vague P, Juhan-Vague I, Aillaud MF, Badier C, Viard R, Alessi MC, Collen D. Correlation between blood fibrinolytic activity, plasminogen activator inhibitor level, plasma insulin level and relative body weight in normal and obese subjects. Metabolism 1986; 35: 250-253
• 17 Legnani C, Maccaferri P, Tonini P, Cassio A, Cacciari E, Coccheri S. Reduced fibrinolytic response in obese children. Association with high baseline activity of the fast acting plasminogen activator inhibitor (PAI-1). Fibrinolysis 1988; 2: 211-214
• 18 Juhan-Vague I, Roul C, Alessi MC, Ardissone JP, Heim M, Vague P. Increased plasminogen activator inhibitor activity in non insulin dependent diabetic patients. Relationship with plasma insulin. Thromb Haemostas 1989; 61: 370-373
• 19 Sundell IB, Nilsson TK, Hallmans G, Hellsten G, Dahlen GH. Interrelationships between plasma levels of plasminogen activator inhibitor, tissue plasminogen activator, lipoprotein (a), and established cardiovascular risk factors in a North Swedish population. Atherosclerosis 1989; 80: 9-16
• 20 Vague P, Juhan-Vague I, Chabert V, Alessi MC, Atland C. Fat distribution and plasminogen activator inhibitor activity in non diabetic obese women. Metabolism 1989; 38: 913-915
• 21 Juhan-Vague I, Alessi MC, Joly P, Thirion X, Vague P, Declerck PJ, Serradimigni A, Collen D. Plasma plasminogen activator inhibitor in angina pectoris. Influence of plasma insulin and acute-phase response. Arteriosclerosis 1989; 9: 362-367
• 22 Landin K, Tengbom L, Smith U. Elevated fibrinogen and plasminogen activator inhibitor 1 (PAI-1) in hypertension are related to metabolic risk factors for cardiovascular disease. J Intern Med 1990; 227: 273-278
• 23 Juhan-Vague I, Aillaud MF, De Cock F, Philip-Joet C, Arnaud C, Serradimigni A, Collen D. The fast-acting inhibitor of tissue-type plasminogen activator is an acute phase reactant protein. In: Progress in Fibrinolysis. Vol VII. Davidson JF, Donati MB, Coccheri S. (eds). Churchill Livingstone; Edinburgh: 1985. pp 146-149
• 24 Aillaud MF, Juhan-Vague I, Alessi MC, Marecal M, Vinson MF, Arnaud C, Vague P, Collen D. Increased plasminogen activator inhibitor (PAI-1) levels in the post-operative period. No cause-effect relation with increased cortisol. Thromb Haemostas 1985; 54: 466-468
• 25 Kluft C, Verheijen JH, Jie AFH, Rijken DC, Preston FE, Sueling HM, Jespersen J, Aasen AO. The postoperative fibrinolytic shutdown: a rapidly reverting acute phase pattern for the fast-acting inhibitor or tissue-type plasminogen activator after trauma. Scand J Clin Lab Invest 1985; 45: 605-610
• 26 Colucci M, Paramo JA, Collen D. Generation in plasma of a fastacting inhibitor of plasminogen activator in response to endotoxin stimulation. J Clin Invest 1985; 75: 818-824
• 27 Gram J, Kluft C, Jespersen J. Depression of tissue plasminogen activator (t-PA) activity and rise of t-PA inhibition and acute phase reactants in blood of patients with acute myocardial infarction (AMI). Thromb Haemostas 1987; 58: 817-821
• 28 Pralong G, Calandra T, Glauser MP, Schellekens J, Verhoef J, Bachmann F, Kruithof EKO. Plasminogen activator inhibitor 1: A new prognostic marker in septic shock. Thromb Haemostas 1989; 61: 459-462
• 29 Brandtzaeg P, Joo GB, Brusletto B, Kierulf P. Plasminogen activator inhibitor 1 and 2, alpha 2 antiplasmin plasminogen, and endotoxin levels in systemic meningococcal disease. Thromb Res 1990; 57: 271-278
• 30 Wiman B, Csemiczky G, Marsk L, Robbe H. The fast inhibitor of tissue plasminogen activator in plasma during pregnancy. Thromb Haemostas 1984; 52: 124-126
• 31 Nilsson IM, Felding P, Lecander I, Lenner C, Astedt B. Different types of plasminogen activator inhibitors in plasma and platelets in pregnant women. Br J Haematol 1986; 62: 215-220
• 32 Kruithof EKO, Tran-Thang C, Gudinchet A, Hauert J, Nicoloso G, Genton C, Welti H, Bachmann F. Fibrinolysis in pregnancy: a study of plasminogen activator inhibitors. Blood 1987; 69: 460-466
• 33 Juhan-Vague I, Alessi MC, Fossat C, Declerck PJ, Kruithof EKO. Plasma determination of plasminogen activator inhibitor 1 antigen must be performed in blood collected on antiplatelet/anticoagulant mixture. Thromb Haemostas 1987; 58: 1096
• 34 Eriksson E, Ranby M, Gyzander E, Risberg B. Determination of plasminogen activator inhibitor plasma using t-PA and a chromogenic single-point poly-D-lysine stimulated assay. Thromb Res 1988; 50: 91-101
• 35 Declerck PJ, Alessi MC, Verstreken M, Kruithof EKO, Juhan-Vague I, Collen D. Measurement of plasminogen activator inhibitor 1 in biological fluids with a murine monoclonal antibody based enzyme linked immunosorbent assay. Blood 1988; 71: 220-225
• 36 Declerck PJ, Verstreken M, Collen D. An immunofunctional assay for active plasminogen activator inhibitor 1 (PAI-1). Fibrinolysis 1988; 2 (Suppl) (02) 17-18
• 37 Alessi MC, Juhan-Vague I, Declerck PJ, Anfosso F, Gueunoun E, Collen D. Correlations between t-PA and PAI-1 antigen and activity and t-PA/PAI-1 complexes in plasma of control subjects and of patients with increased t-PA or PAI-1 levels. Thromb Res 1990; 60: 509-516
• 38 Clauss A. Gerinnungsphysiologische Schnellmethode zur Bestimmung des Fibrinogens. Acta Haematol 1957; 17: 237-246
• 39 Yalow RS, Glick SM, Roth J, Berson SA. Plasma insulin and growth hormone levels in obesity and diabetes. Ann NY Acad Sci 1965; 131: 357-373
• 40 Juhan-Vague I, Alessi MC, Vague P. Increased plasma concentration of plasminogen activator inhibitor 1. A possible link between insulin resistance and athero thrombosis. Diabetologia 1991; 34: 457-462
• 41 Emeis JJ, Kooistra T. Interleukin I and lipopolysaccharide induce an inhibitor of tissue-type plasminogen activator in vivo and in cultured endothelial cells. J Exp Med 1986; 163: 1260-1266
• 42 Dosne AM, Dubor F, Chedid L. Plasminogen activator inhibitor induced by lipopolysaccharide injection in the rat. Fibrinolysis 1987; 1: 45-49
• 43 Van Hinsbergh VWM, Kooistra T, van den Berg EA, Princen HMG, Fiers W, Emeis JJ. Tumor necrosis factor increases the production of plasminogen activator inhibitor in human endothelial cells in vitro and in rats in vivo. Blood 1988; 72: 1467-1473
• 44 Medcalf RL, Kruithof EKO, Schleuning WD. Plasminogen activator inhibitor 1 and 2 are tumor necrosis factor/cachectin responsive genes. J Exp Med 1988; 168: 751-759
• 45 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
• 46 Alessi MC, Juhan-Vague I, Kooistra T, Declerck PJ, Collen D. Insulin stimulates the synthesis of plasminogen activator inhibitor 1 by the human hepatocellular cell line Hep G2. Thromb Haemostas 1988; 60: 491-494
• 47 Kooistra T, Bosma P, Tons H, van den Berg A, Meyer P, Princen H. Plasminogen activator inhibitor 1: Biosynthesis and mRNA levels are increased by insulin in cultured human hepatocytes. Thromb Haemostas 1989; 62: 723-728
• 48 Gelehrter TD, Sznycer-Laszuk R, Zeheb R, Cwikel BJ. Dexa-methasone inhibitor of tissue type plasminogen activator (t-PA) activity: Paradoxical induction of both t-PA antigen and plasminogen activator inhibitor. Mol Endocrinol 1987; 1: 97-101
• 49 Latron Y, Alessi MC, Anfosso F, Nalbonne G, Lafont H, Juhan-Vague I. Effect of low density lipoproteins on secretion of plasminogen activator inhibitor 1 (PAI-1) by human endothelial cells and hepatoma cells. Fibrinolysis 1990; 4 (Suppl) (02) 82-83
• 50 Bolli GB. The dawn phenomenon: its origin and contribution to early morning hyperglycemia in diabetes mellitus. Diab Metabol 1988; 14: 675-686
• 51 Cincotta AH, Meier AH. Prolactin permits the expression of a circadian variation in lipogenic responsiveness to insulin in hepato-cytes of the golden hamster (mesocricetus auratus). J Endocrinol 1985; 106: 173-176
• 52 Hung CT, Beyer J, Schulz G. Fasting and feeding variations of insulin requirements and insulin binding to erythrocytes at different times of the day in insulin dependent diabetics. Assessed under the condition of glucose controlled insulin infusion. Horm Metabol Res 1986; 18: 466-469
• 53 Cincotta AH, Meier AH. Prolactin influences the circadian rhythm of lipogenesis in primary cultured hepatocytes. Horm Metabol Res 1989; 21: 64-68
• 54 Gralnick HR, Mac Keown LP, Wilson OM, Williams SB, Elin RJ. Von Willebrand factor release induced by endotoxin. J Lab Clin Med 1989; 113: 118-122
• 55 Beisei WR, Bruton J, Anderson KD, Sawyer WD. Adrenocortical responses during tularemia in human subjects. J Clin Endocrinol 1967; 27: 61-69
• 56 Sherman B, Wysham C, Pfohl B. Age-related changes in the circadian rhythm of plasma cortisol in man. J Clin Endocrinol Metab 1985; 61: 439-443
• 57 Peternel P, Stegnar M, Salobir U, Salobir B, Keber D, Vene N. Shift work and circadian rhythm of blood fibrinolytic parameters. Fibrinolysis 1990; 4 (Suppl) [phone]
• 58 Feinberg RF, Kao LC, Haimowitz JE, Queenan JT, Wun TC, Strauss JF, Kliman HJ. Plasminogen activator inhibitor types 1 and 2 in human trophoblasts. PAI-1 is an immunocytochemical marker of invading trophoblasts. Lab Invest 1989; 61: 20-26