Subscribe to RSS
Please copy the URL and add it into your RSS Feed Reader.
https://www.thieme-connect.de/rss/thieme/en/10.1055-s-00000077.xml
Semin Thromb Hemost 2000; 26(5): 495-502
DOI: 10.1055/s-2000-13205
DOI: 10.1055/s-2000-13205
Impaired Endogenous Fibrinolysis in Diabetes Mellitus: Mechanisms and Therapeutic Approaches
Further Information
Publication History
Publication Date:
31 December 2000 (online)
ABSTRACT
In type II diabetes mellitus the activity of the endogenous fibrinolytic system is reduced secondary to increased plasma activity of the plasminogen activator inhibitor type 1 (PAI-1). Because PAI-1 is considered an independent risk factor for cardiovascular disease, increased PAI-1 activity in diabetes mellitus may partly explain the increased susceptibility to both primary atherosclerosis and restenosis after angioplasty in this disease. The factors contributing to increased PAI-1 expression in diabetes mellitus are reviewed as well as possible therapeutic approaches to normalize increased PAI-1 expression.
KEYWORD
Plasminogen activator inhibitor - PAI-1 - hyperglycemia - hyperinsulinemia - endothelium
REFERENCES
- 1 Andreotti F, Davies G J, Hackett D R. Major circadian fluctuations in fibrinolytic factors and possible relevance to time of onset of myocardial infarction, sudden cardic death and stroke. Am J Cardiol . 1988; 62 635-637
- 2 Angleton P, Chandler W L, Schmer G. Diurnal variation of tissue-type plasminogen activator and its rapid inhibitor (PAI-1). Circulation . 1989; 79 101-106
- 3 Krishnamurti C, Barr C F, Hassett M A, Young G D, Alving B M. Plasminogen activator inhibitor: A regulator of ancrod-induced fibrin deposition in rabbits. Blood . 1987; 69 798-803
- 4 Vaughan D E, Declerck P J, van Houtte E, de Mol M, Collen D. Reactivated recombinant plasminogen activator inhibitor-1 (rPAI-1) effectively prevents thrombolysis in vivo. Thromb Haemost . 1992; 68 60-63
- 5 Levi M, Biemond B J, van Zonneveld J A, Wouter ten Cate J, Pannekoek H. Inhibition of plasminogen activator inhibitor-1 activity results in promotion of endogenous thrombolysis and inhibition of thrombus extension in models of experimental thrombosis. Circulation . 1992; 85 305-312
- 6 Erickson L A, Fici G J, Lund J E. Development of venous occlusions in mice transgenic for the plasminogen activator inhibitor-1 gene. Nature . 1990; 346 74-76
- 7 Carmeliet P, Stassen J M, Schoonjans L. Plasminogen activator inhibitor-1 gene-deficient mice. II. Effects on hemostasis, thrombosis, and thrombolysis. J Clin Invest . 1993; 92 2756-2760
- 8 Reilly C F, Fujita T, Hutzelmann J E, Mayer E J, Shebuski R J. Plasminogen activator inhibitor-1 suppresses endogenous fibrinolysis in a canine model of pulmonary embolism. Circulation . 1991; 84 287-292
- 9 Aznar J, Estellés A, Tormo G. Plasminogen activator inhibitor activity and other fibrinolytic variables in patients with coronary artery disease. Br Heart J . 1988; 59 535-541
- 10 Olofsson B O, Dahlén G, Nilsson T K. Evidence for increased levels of plasminogen activator inhibitor and tissue plasminogen activator in plasma of patients with angiographically verified coronary artery disease. Eur Heart J . 1989; 10 77-82
- 11 Huber K, Jörg M, Probst P. A decrease in plasminogen activator-1 activity after successful percutaneous transluminal coronary angioplasty is associated with a significantly reduced risk for coronary restenosis. Thromb Haemost . 1992; 67 209-213
- 12 Verheugt F WA, ten Cate W J, Sturk A. Tissue plasminogen activator activity and inhibition in acute myocardial infarction and angiographically normal coronary arteries. Am J Cardiol . 1987; 59 1075-1079
- 13 Hamsten A, Wiman B, de Faire U, Blombäck M. Increased plasma levels of a rapid inhibitor of tissue plasminogen activator in young survivors of myocardial infarction. N Engl J Med . 1985; 313 1557-1563
- 14 Hamsten A, de Faire U, Waldius G. Plasminogen activator inhibitor in plasma: Risk factor for recurrent myocardial infarction. Lancet . 1987; 2 3-8
- 15 Salomaa V, Stinson V, Kark J D. Association of fibrinolytic parameters with early atherosclerosis. The ARIC study. Circulation . 1995; 91 284-290
- 16 Cortellaro M, Cofrancesco E, Boschetti C. Increased fibrin turnover and high PAI-1 activity as predictors of ischemic events in atherosclerotic patients. A case-control study. Arterioscler Thromb . 1993; 13 1412-1417
- 17 Wiman B, Hamsten A. The fibrinolytic enzyme system and its role in the etiology of thromboembolic disease. Semin Thromb Hemost . 1990; 16 207-216
- 18 Grimaudo V, Bachmann F, Hauert J, Christe M A, Kruithof E KO. Hypofibrinolysis in patients with a history of idiopathic deep vein thrombosis and/or pulmonary embolism. Thromb Haemost . 1992; 67 397-401
- 19 Barbash G I, Hod H, Roth A. Correlation of baseline plasminogen activator inhibitor activity with patency of the infarct artery after thrombolytic therapy in acute myocardial infarction. Am J Cardiol . 1989; 64 1231-1235
- 20 Sane D C, Stump D C, Topol E J. Correlation between baseline plasminogen activator inhibitor levels and clinical outcome during therapy with tissue plasminogen activator for acute myocardial infarction. Thromb Haemost . 1991; 65 275-279
- 21 Nordt T K, Moser M, Kohler B. Augmented platelet aggregation as predictor of reocclusion after thrombolysis in acute myocardial infarction. Thromb Haemost . 1998; 80 881-886
- 22 Schleef R R, Higgins D L, Pillemer E, Levitt L J. Bleeding diathesis due to decreased functional activity of type 1 plasminogen activator inhibitor. J Clin Invest . 1989; 83 1747-1752
- 23 Diéval J, Nguyen G, Gross S, Delobel J, Kruithof E KO. A lifelong bleeding disorder associated with a deficiency of plasminogen activator inhibitor type 1. Blood . 1991; 77 528-532
- 24 Fay W P, Shapiro A D, Shih J L, Schleef R R, Ginsburg D. Complete deficiency of plasminogen activator inhibitor type 1 due to a frame-shift mutation. N Engl J Med . 1992; 327 1729-1733
- 25 Lee M H, Vosburgh E, Anderson K, McDonagh J. Deficiency of plasma plasminogen activator inhibitor 1 results in hyperfibrinolytic bleeding. Blood . 1993; 81 2357-2362
- 26 Nordt T K, Peter K, Ruef J, Kübler W, Bode C. Plasminogen activator inhibitor type-1 (PAI-1) and its role in cardiovascular disease. Thromb Haemost . 1999; 82(Suppl) 14-18
- 27 Factor S M, Segal B H, van Hoeven H K. Diabetes and coronary artery disease. Coronary Artery Dis . 1992; 3 4-10
- 28 Califf R M, Fortin D F, Frid D J. Restenosis after coronary angioplasty: An overview. J Am Coll Cardiol . 1991; 17 2B-13B
- 29 Sobel B E. Potentiation of vasculopathy by insulin: Implications from an NHLBI Clinical Alert. Circulation . 1996; 93 1613-1615
- 30 The Bypass Angioplasty Revascularization Investigation (BARI) Investigators. Comparison of coronary bypass surgery with angioplasty in patients with multivessel disease. N Engl J Med . 1996; 335 217-225
- 31 Juhan-Vague I, Alessi M C, Vague P. Increased plasma plasminogen activator inhibitor 1 levels. A possible link between insulin resistance and atherothrombosis. Diabetologia . 1991; 34 457-462
- 32 Schneider D J, Nordt T K, Sobel B E. Attenuated fibrinolysis and accelerated atherosclerosis in type II diabetic patients. Diabetes . 1993; 42 1-7
- 33 Falk E, Shah P K, Fuster V. Coronary plaque disruption. Circulation . 1995; 92 657-671
- 34 Bakker C M, Metselaar H J, Groenland T N. Increased tissue-type plasminogen activator activity in orthotopic but not heterotopic liver transplantation: The role of the anhepatic period. Hepatology . 1992; 16 404-408
- 35 Kooistra T. The use of cultured human endothelial cells and hepatocytes as an in vitro model system to study modulation of endogenous fibrinolysis. Fibrinolysis . 1990; 4(Suppl 2) 33-39
- 36 Maiello M, Boeri D, Podesta F. Increased expression of tissue plasminogen activator and its inhibitor and reduced fibrinolytic potential of human endothelial cells cultured in elevated glucose. Diabetes . 1992; 41 1009-1015
- 37 Cagliero E, Roth T, Roy S, Maiello M, Lorenzi M. Expression of genes related to the extracellular matrix in human endothelial cells. J Biol Chem . 1991; 266 14244-14250
- 38 Nordt T K, Klassen K J, Schneider D J, Sobel B E. Augmentation of synthesis of plasminogen activator inhibitor type-1 in arterial endothelial cells by glucose and its implications for local fibrinolysis. Arterioscler Thromb . 1993; 13 1822-1828
- 39 Hughes H H. Swine in cardiovascular research. Lab Anim Sci . 1986; 36 348-350
- 40 van Hinsbergh W M V, Binnema D, Scheffer M A. Production of plasminogen activators and inhibitor by serially propagated endothelial cells from adult human blood vessels. Arteriosclerosis . 1987; 7 389-400
- 41 Nordt T K, Schneider D J, Sobel B E. Augmentation of the synthesis of plasminogen activator inhibitor type-1 (PAI-1) by precursors of insulin: A potential risk factor for vascular disease. Circulation . 1994; 89 321-330
- 42 Sobey W J, Beer S F, Carrington C A. Sensitive and specific two-site immunoradiometric assays for human insulin, proinsulin, 65-66 split and 32-33 split proinsulins. Biochem J . 1989; 260 535-541
- 43 Bowsher R R, Wolny J D, Frank B H. A rapid and sensitive radioimmunoassay for the measurement of proinsulin in human serum. Diabetes . 1992; 41 1084-1090
- 44 Temple R C, Clark P MS, Nagi D K. Radioimmunoassay may overestimate insulin in non-insulin-dependent diabetics. Clin Endocrinol . 1990; 32 689-693
- 45 Nagi D K, Hendra T J, Ryle A J. The relationships of concentrations of insulin, intact proinsulin and 32-33 split proinsulin with cardiovascular risk factors in type 2 (non-insulin-dependent) diabetic subjects. Diabetologia . 1990; 33 532-537
- 46 Heding L G. Determination of total serum insulin (IRI) in insulin-treated diabetic patients. Diabetologia . 1972; 8 260-266
- 47 Alessi M C, Juhan-Vague I, Kooistra T, Declerck P J, Collen D. Insulin stimulates the synthesis of plasminogen activator inhibitor 1 by the human hepatocellular cell line Hep G2. Thromb Haemost . 1988; 60 491-494
- 48 Kooistra T, Bosma P J, Töns H AM. Plasminogen activator inhibitor 1: Biosynthesis and mRNA level are increased by insulin in cultured human hepatocytes. Thromb Haemost . 1989; 62 123-128
- 49 Schneider D J, Sobel B E. Augmentation of synthesis of plasminogen activator inhibitor type 1 by insulin and insulin-like growth factor type I: Implications for vascular disease in hyperinsulinemic states. Proc Natl Acad Sci USA . 1991; 88 9959-9963
- 50 Spradlin C T, Galloway J A, Anderson J H. Apparent increase in coronary heart disease with human proinsulin (HPI): Randomization failure or HPI effect?. Diabetologia . 1990; 33(Suppl) A60
- 51 Galloway J A, Hooper S A, Spradlin C T. Biosynthetic human proinsulin. Review of chemistry, in vitro and in vivo receptor binding, animal and human pharmacology studies, and clinical trial experience. Diabetes Care . 1992; 15 666-692
- 52 Jain S K, Nagi D K, Slavin B M, Lumb P J, Yudkin J S. Insulin therapy in type 2 diabetic subjects suppresses plasminogen activator inhibitor (PAI-1) avtivity and proinsulin-like molecules independently of glycemic control. Diabetic Med . 1993; 10 27-32
- 53 Misbin R I, Merimee T J, Lowenstein J M. Insulin removal by isolated perfused rat liver. Am J Physiol . 1976; 230 171-177
- 54 Glauber H S, Henry R R, Wallace P. The effects of biosynthetic human proinsulin on carbohydrate metabolism in non-insulin-dependent diabetes mellitus. N Engl J Med . 1987; 316 443-449
- 55 Nordt T K, Sawa H, Fujii S, Sobel B E. Induction of plasminogen activator inhibitor type-1 (PAI-1) by proinsulin and insulin in vivo. Circulation . 1995; 91 764-770
- 56 Fujii S, Sobel B E. Induction of plasminogen activator inhibitor by products released from platelets. Circulation . 1990; 82 1485-1493
- 57 Nordt T K, Sawa H, Fujii S, Sobel B E. Hyperinsulinemia increases plasma activity of PAI-1 in vivo independently of an acute phase reaction. Fibrinolysis . 1997; 11(Suppl 1) 51-54
- 58 Nordt T K, Sawa H, Fujii S, Bode C, Sobel B E. Augmentation of arterial endothelial cell expression of the plasminogen activator inhibitor type-1 (PAI-1) gene by proinsulin and insulin in vivo. J Mol Cell Cardiol . 1998; 30 1535-1543
- 59 Grant P J, Kruithof E KO, Felley C P, Felber J P, Bachmann F. Short-term infusions of insulin, triacylglycerol and glucose do not cause acute increases in plasminogen activator inhibitor-1 conmcentratiosn in man. Clin Sci . 1990; 79 513-516
- 60 Landin K, Tengborn L, Chmielewska J, von Schenck H, Smith U. The acute effect of insulin on tissue plasminogen activator and plasminogen activator inhibitor in man. Thromb Haemost . 1991; 65 130-133
- 61 Vuorinen-Markkola H, Puhakainen I, Yki-Järvinen H. No evidence for short-term regulation of plasminogen activator inhibitor activity by insulin in man. Thromb Haemost . 1992; 67 117-120
- 62 Potter van Loon J B, de Bart C W A, Radder J K. Acute exogenous hyperinsulinaemia does not result in elevation of plasma plasminogen activator inhibitor-1 (PAI-1) in humans. Fibrinolysis . 1990; 4(Suppl 2) 93-94
- 63 Frick M H, Elo O, Haapa K. Helsinki Heart Study: Primary prevention trial with gemfibrozil in middle-aged men with dyslipidemia. Safety of treatment, changes in risk factors, and incidence of coronary heart disease. N Engl J Med . 1987; 317 1237-1245.
- 64 Manninen V, Elo M O, Frick M H. Lipid alterations and decline in the incidence of coronary heart disease in the Helsinki Heart Study. JAMA . 1988; 260 641-651
- 65 Tenkanen L, Mänttäri M, Manninen V. Some coronary risk factors related to the insulin resistance syndrome and treatment with gemfibrozil. Experience from the Helsinki Heart Study. Circulation . 1995; 92 1779-1785
- 66 Huttunen J K, Heinonen O P, Manninen V. The Helsinki Heart Study: An 8.5-year safety and mortality follow-up. J Intern Med . 1994; 235 31-39
- 67 Avellone G, Di Garbo V, Panno A V. Changes induced by gemfibrozil on lipidic, coagulative and fibrinolytic pattern in patients with type IV hyperlipoproteinemia. Int Angiol . 1988; 7 270-277
- 68 Andersen P, Smith P, Seljeflot I, Brataker S, Arnesen H. Effects of gemfibrozil on lipids and haemostasis after myocardial infarction. Thromb Haemost . 1990; 63 174-177
- 69 Nordt T K, Kornas K, Peter K. Attenuation by gemfibrozil of expression of plasminogen activator inhibitor type-1 induced by insulin and its precursors. Circulation . 1997; 95 677-683
- 70 Nilsson L, Takemura T, Eriksson P, Hamsten A. Effects of fibrate compounds on expression of plasminogen activator inhibitor-1 by cultured endothelial cells. Arterioscler Thromb Vasc Biol . 1999; 19 1577-1581
- 71 Keber I, Lavre J, Suc S, Keber D. The decrease of plasminogen activator inhibitor after normalization of triglycerides during treatment with fibrates. Fibrinolysis . 1994; 8(Suppl 2) 57-59
- 72 Bröijersen A, Eriksson M, Wiman B, Angelin B, Hjemdahl P. Gemfibrozil treatment of combined hyperlipoproteinemia. No improvement of fibrinolysis despite marked reduction of plasma triglyceride levels. Arterioscler Thromb Vasc Biol . 1996; 16 511-516
- 73 Cimminiello C, Vigorelli P, Piliego T. Fibrinolytic response in subjects with hypertriglyceridemia and low HDL cholesterol. Biomed Pharmacother . 1997; 51 164-169
- 74 Kockx M, de Maat P M M, Knipscheer H C. Effects of gemfibrozil and ciprofibrate on plasma levels of tissue-type plasminogen activator, plasminogen activator inhibitor-1 and fibrinogen in hyperlipidemic patients. Thromb Haemost . 1997; 78 1167-1172
- 75 Jeng J R, Jeng C Y, Sheu W H. Gemfibrozil treatment of hypertriglyceridemia: improvement on fibrinolysis without change of insulin resistance. Am Heart J . 1997; 134 565-571
- 76 Pazzucconi F, Mannucci L, Mussoni L. Bezafibrate lowers plasma lipids, fibrinogen and platelet aggregability in hypertriglyceridemia. Eur J Clin Pharmacol . 1992; 43 219-223