Advertisement

Diabetes and Thrombosis

  • David J. Schneider
  • Burton E. Sobel
Part of the Contemporary Cardiology book series (CONCARD)

Abstract

Complications of macrovascular disease, referred to by some as atherothrombosis, are responsible for 50% of the deaths in patients with type 2 diabetes mellitus, 27% of the deaths in patients with type 1 diabetes for 35 years or less, and 67% of the deaths in patients with type 1 diabetes for 40 years or more (1,2). The rapid progression of macroangiopathy in patients with type 2 diabetes may reflect diverse phenomena: some intrinsic to the vessel wall; angiopathic factors such as elevated homocysteine and hyperlipidemia; deleterious effects of dysinsulinemia; and excessive or persistent microthrombi with consequent acceleration of vasculopathy secondary to clot-associated mitogens (3,4). As a result of their adverse effects, cardiovascular mortality is as high as 15% in the 10 years after the diagnosis of diabetes mellitus becomes established (5). Because more than 90% of patients with diabetes have type 2 diabetes and because macrovascular disease is the cause of death in most patients with type 2 as opposed to type 1 (insulinopenic) diabetes, type 2 diabetes will be the focus of our discussion.

Keywords

Plasminogen Activator Plaque Rupture Plasminogen Activator Inhibitor Type Fibrinolytic System Macrovascular Disease 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Geiss LS, Herman WH, Smith PJ. Mortality in non–insulin–dependent diabetes. In: Harris MI, Cowie CC, Stern MP, Boyko EJ, Reiber GE, Bennet PH, eds. Diabetes in America. DHHS NIH Publication no. 95–1468. U.S. Government Printing Office, Washington DC, 1995, pp. 233–257.Google Scholar
  2. 2.
    Portuese E, Orchard T. Mortality in insulin–dependent diabetes. In: Harris MI, Cowie CC, Stern MP, Boyko EJ, Reiber GE, Bennet PH, eds. Diabetes in America. DHHS NIH Publication no. 95–1468. U.S. Government Printing Office, Washington DC, 1995, pp. 221–232.Google Scholar
  3. 3.
    Sobel BE. Coronary artery disease and fibrinolysis: from the blood to the vessel wall. Thrombosis and Haemostasis 1999;82:8–13.PubMedGoogle Scholar
  4. 4.
    Schneider DJ, Sobel BE. Determinants of coronary vascular disease in patients with type II diabetes mellitus and their therapeutic implications. Clin Cardiol 1997;20:433–440.PubMedCrossRefGoogle Scholar
  5. 5.
    Uusitupa MIJ, Niskanen LK, Siitonen O, Voutilainen E, Pyorala K. Ten–year cardiovascular mortality in relation to risk factors and abnormalities in lipoprotein composition in type 2 (non–insulin–depen dent) diabetic and non–diabetic subjects. Diabetologia 1993;36:1175–1184.PubMedCrossRefGoogle Scholar
  6. 6.
    Kornowski R, Mintz GS, Kent KM, et al. Increased restenosis in diabetes mellitus after coronary interventions is due to exaggerted intimal hyperplasia. Circulation 1997;95:1366–1369.PubMedCrossRefGoogle Scholar
  7. 7.
    Velican C, Velican D. The precursors of coronary atherosclerotic plaques in subjects up to 40 years old. Atherosclerosis 1980;37:33–46.PubMedCrossRefGoogle Scholar
  8. 8.
    Spurlock BO, Chandler AB. Adherent platelets and surface microthrombi of the human aorta and left coronary artery: a scanning electron microscopy feasibility study. Scanning Microsc 1987;1:1359–1365.PubMedGoogle Scholar
  9. 9.
    Ambrose JA, Tannenbaum AM, Alexpoulos D, et al. Angiographic progression of coronary artery disease and the development of myocardial infarction. J Am Coll Cardiol 1988;12:56–62.PubMedCrossRefGoogle Scholar
  10. 10.
    Little WC, Constantinescu M, Applegate RJ, et al. Can coronary angiography predict the site of a subsequent myocardial infarction in patients with mild–to–moderate coronary artery disease? Circulation 1988;78:1157–1166.PubMedCrossRefGoogle Scholar
  11. 11.
    Davies MJ, Richardson PD, Woolf N, Kratz DR, Mann J. Risk of thrombosis in human atherosclerotic plaques role of extracellular lipid, macrophage, and smooth muscle content. Br Heart J 1993;69:377–381.PubMedCrossRefGoogle Scholar
  12. 12.
    Falk E, Shah PK, Fuster V. Coronary plaque disruption. Circulation 1995;92:657–671.PubMedCrossRefGoogle Scholar
  13. 13.
    Nemerson Y. Tissue factor and hemostasis. Blood 1988;71:1–8.PubMedGoogle Scholar
  14. 14.
    Rand MD, Lock JB, Veer CV, Gaffney DP, Mann KG. Blood clotting in minimally altered whole blood. Blood 1996;88:3432–3445.PubMedGoogle Scholar
  15. 15.
    Monroe DM, Roberts HR, Hoffman M. Platelet procoagulant complex assembly in a tissue factorinitiated system. Br J Haemotol 1994;88:364–371.CrossRefGoogle Scholar
  16. 16.
    Staatz WD, Rajpara SM, Wayner EA, Carter WG, Santoro SA. The membrane glycoprotein Ia–IIa (VLA–2) complex mediates the Mg’2–dependent adhesion of platelets to collagen. J Cell Bio11989;108: 1917–1921.Google Scholar
  17. 17.
    Kroll MH, Harris TS, Moake JL, Handin RI, Schafer AI. von Willebrand factor binding to platelet GP lb initiates signals for platelet activation. J Clin Invest 1991;88:1568–1573.PubMedCrossRefGoogle Scholar
  18. 18.
    Sims PJ, Ginsberg MH, Plow EF, Shattil SJ. Effect of platelet activation on the conformation of the plasma membrane glycoprotein Ilb–IIIa complex. J Biol Chem 1991;266:7345–7352.PubMedGoogle Scholar
  19. 19.
    Monroe DM, Roberts HR, Hoffman M. Platelet procoagulant complex assembly in a tissue factorinitiated system. Br J Haemotol 1994;88:364–371.CrossRefGoogle Scholar
  20. 20.
    Schwartz CJ, Valente AJ, Kelley JL, Sprague EA, Edwards EH. Thrombosis and the development of atherosclerosis: Roditansky revisited. Semin Thromb Hemost 1988;14:189–195.PubMedCrossRefGoogle Scholar
  21. 21.
    Stirk CM, Kochhar A, Smith EB, Thompson WD. Presence of growth–stimulating fibrin–degradation products containing fragment E in human atherosclerotic plaques. Atherosclerosis 1993;103:159–169.CrossRefGoogle Scholar
  22. 22.
    Ross R. The pathogenesis of atherosclerosis: a perspective for the 1990s. Nature 1993;362:801–809.PubMedCrossRefGoogle Scholar
  23. 23.
    Scharf RE, Harker LA. Thrombosis and atherosclerosis: regulatory role of interactions among blood components and endothelium. Blut 1987;55:131–144.PubMedCrossRefGoogle Scholar
  24. 24.
    Bar–Shavit R, Hruska KA, Kahn AJ, Wilner GD. Hormone–like activity of human thrombin. Ann NY Acad Sci 1986;485:335–348.CrossRefGoogle Scholar
  25. 25.
    Jawien A, Bowen–Pope DF, Lindner V, Schwartz SM, Clowes AW. Platelet–derived growth factor promotes smooth muscle migration and intimal thickening in a rat model of balloon angioplasty. J Clin Invest 1992;89:507–511.PubMedCrossRefGoogle Scholar
  26. 26.
    Friedman RJ, Stemerman MB, Wenz B, et al. The effect of thrombocytopenia on experimental arteriosclerotic lesion formation in rabbits. Smooth muscle proliferation and re–endothelialization. J Clin Invest 1977;60:1191–1201.PubMedCrossRefGoogle Scholar
  27. 27.
    Fernandez–Ortiz AJ, Badimon JJ, Falk E, et al. Characterization of relative thrombogenicity of atherosclerotic plaque components: implications for consequences of plaque rupture. J Am Coll Cardiol 1994;23:1562–1569.CrossRefGoogle Scholar
  28. 28.
    Brown AS, Hong Y, de Belder A, et al. Megakaryoctye ploidy and platelet changes in human diabetes and atherosclerosis. Arterioscler Thromb Vasc Biol 1997;17:802–807.PubMedCrossRefGoogle Scholar
  29. 29.
    Oskarsson HJ, Hofmeyer TG. Platelets from patients with diabetes mellitus have impaired ability to mediate vasodilatation. J Am Coll Cardiol 1996;27:1464–1470.PubMedCrossRefGoogle Scholar
  30. 30.
    Oskarsson HJ, Hofmeyer TG. Diabetic human platelets release a substance that inhibits plateletmediated vasodilatation. Am J Physiol 1997;273:H371–H379.Google Scholar
  31. 31.
    Winocour PD, Watala C, Kinlough–Rathbone, RL. Membrane fluidity is related to the extent of glycation of proteins, but not to alterations in the cholesterol to phospholipid molar ratio in isolated platelet membranes from diabetic and control subjects. Thromb Haemost 1992;67:567–571.PubMedGoogle Scholar
  32. 32.
    Davi G, Catalano I, Averna M, Notarbartolo A, Ciabottoni G, Patrono C. Thromboxane biosynthesis and platelet function in type II diabetes mellitus. N Engl J Med 1990;322:1769–1774.PubMedCrossRefGoogle Scholar
  33. 33.
    Ishii H, Umeda F, Nawata H. Platelet function in diabetes mellitus. Diabetes Metab Rev 1992;8:53–66.PubMedCrossRefGoogle Scholar
  34. 34.
    Hendra T, Betteridge DJ. Platelet function, platelet prostanoids and vascular prostacyclin in diabetes. Prostaglandins Leukot Essent Fatty Acids 1989;35:197–212.PubMedCrossRefGoogle Scholar
  35. 35.
    Menys VS, Bhatnagar D, Mackness MI, Durrington PN. Spontaneous platelet aggregation in whole blood is increased in non-insulin-dependent diabetes mellitus and in female but not male patients with primary dyslipidemia. Atherosclerosis 1995;112:115–122.PubMedCrossRefGoogle Scholar
  36. 36.
    Sugimoto H, Franks DJ, Lecavalier L, Chiasson JL, Hamet P. Therapeutic modulation of growth-promoting activity in platelets from diabetics. Diabetes 1987;36:667–672.PubMedCrossRefGoogle Scholar
  37. 37.
    Koschinsky T, Bunting CR, Rutter R, Gries FA. Vascular growth factors and the development of macrovascular disease in diabetes mellitus. Diabetes Metab 1987;13:318–325.Google Scholar
  38. 38.
    Winocour PD, Bryszewska M, Watala C, et al. Reduced membrane fluidity in platelets from diabetic patients. Diabetes 1990;39:241–244.PubMedCrossRefGoogle Scholar
  39. 39.
    Rao AK, Goldberg RE, Walsh PN. Platelet coagulation activity in diabetes mellitus. Evidence for relationship between platelet coagulant hyperactivity and platelet volume. J Lab Clin Med 1984;103: 82–92.PubMedGoogle Scholar
  40. 40.
    Lupu C, Calb M, Ionescu M, Lupu F. Enhanced prothrombin and intrinsic factor X activation on blood platelets from diabetic patients. Thromb Haemost 1993;70:579–583.PubMedGoogle Scholar
  41. 41.
    Tschoepe D, Roesen P, Esser J, et al. Large platelets circulate in an activated state in diabetes mellitus. Semin Thromb Hemost 1991;17:433–438.PubMedCrossRefGoogle Scholar
  42. 42.
    Tschoepe D, Driesch E, Schwippert B, Nieuwenhuis K, Gries FA. Exposure of adhesion molecules on activated platelets in patients with newly diagnosed IDDM is not normalized by near-normoglycemia. Diabetes 1995;44:890–894.PubMedCrossRefGoogle Scholar
  43. 43.
    Ton–Brown SR, Sobel BE. Plasminogen activator inhibitor is elevated in plasma and diminished in platelets in patients with diabetes mellitus. Thromb Res 1994;75:473–477.CrossRefGoogle Scholar
  44. 44.
    Colwell JA. Vascular thrombosis in type II diabetes mellitus. Diabetes 1993;42:8–11.PubMedGoogle Scholar
  45. 45.
    Kinlough-Rathbone RL, Packham MA, Mustard JF. Vessel injury, platelet adherence, and platelet survival. Arteriosclerosis 1983;3:529–546.PubMedCrossRefGoogle Scholar
  46. 46.
    Winocour PD, Richardson M, Kinlough-Rathbone RL. Continued platelet interaction with de-endothelialized aortae of spontaneously diabetic BB Wistar rats is associated with slow re-endothelialiation and extensive intimal hyperplasia. Int J Exp Pathol 1993;74:603–613.PubMedGoogle Scholar
  47. 47.
    Winocour PD, Watala C, Perry DW, Kinlough-Rathbone RL. Reduced fluidity and increased glycation of membrane proteins of platelets from diabetic subjects are not associated wih increased platelet adherence to glycated collagen. J Lab Clin Med 1992;120:921–928.PubMedGoogle Scholar
  48. 48.
    Tschoepe D, Roesen P, Kaufmann L, Schauseil S, Ostermann H, Gries FA. Evidence for impaired glycoprotein receptor expression on diabetic platelets. Eur J Clin Invest 1990;20:166–170.PubMedCrossRefGoogle Scholar
  49. 49.
    Tschoepe D, Roesen P, Gries FA. Increase in the cytosolic concentration of calcium in platelets of diabetics type II. Thromb Res 1991;62:421–438.CrossRefGoogle Scholar
  50. 50.
    Ishi H, Umeda F, Hashimoto T, Nawata H. Changes in phosphoinositied turnover, Ca2’ mobilization, and protein phosphorylation in platelets from NIDDM patients. Diabetes 1990;39:1561–1568.CrossRefGoogle Scholar
  51. 51.
    Trovati M, Anfossi G, Massucco P, et al. Insulin stimulates nitric oxide synthesis in human platelets and, through nitric oxide, increases platelet concentrations of both guanosine-3’,5’-cyclic monophosphate and adenosine-3’,5’-cyclic monophosphate. Diabetes 1997;46:742–749.PubMedCrossRefGoogle Scholar
  52. 52.
    Marina V, Bruno GA, Trucco F, et al. Platelet cNOS activity is reduced in patients with IDDM and NIDDM. Thromb Haemost 1998;79:520–522.Google Scholar
  53. 53.
    WinocourPD,Kinlough-RathboneRL,MustardJF.Pathwaysresponsibleforplatelethypersensitivity in rats with diabetes. II. Spontaneous diabetes in BB Wistar rats. J Lab Clin Med 1986;109:154–158.Google Scholar
  54. 54.
    Kleiman NS, Lincoff M, Keriakes DJ, et al. Diabetes mellitus, glycoprotein IIB/IIIa blockade and heparin: evidence for a complex interaction in a multicenter trial. Circulation 1998;97:1912–1920.PubMedCrossRefGoogle Scholar
  55. 55.
    Grundy SM, Bilheimer D, Chait A, et al. Summary of the Second Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel II). JAMA 1993;269:3015–3023.CrossRefGoogle Scholar
  56. 56.
    Scharfstein JS, Abendschein DR, Eisenberg PR, et al. Usefulness of fibrinogenolytic and procoagulant markers during thrombolytic therapy in predicting clinical outcomes in acute myocardial infarction. Am J Cardiol 1996;78:503–510.PubMedCrossRefGoogle Scholar
  57. 57.
    Jones RL. Fibrinopeptide-A in diabetes mellitus. Relation to levels of blood glucose, fibrinogen disappearance, and hemodynamic changes. Diabetes 1985;34:836–843.PubMedCrossRefGoogle Scholar
  58. 58.
    Librenti MC, D’Angelo A, Micossi P, Garimberti B, Mannucci PM, Pozza G. Beta-thromboglobulin and fibrinopeptide A in diabetes mellitus as markers of vascular damage. Acta Diabetol Lat 1985;22: 39–45.PubMedCrossRefGoogle Scholar
  59. 59.
    Marongiu F, Conti M, Mameli G, et al. Is the imbalance between thrombin and plasmin activity in diabetes related to the behaviour of antiplasmin activity? Thromb Res 1990;58:91–99.PubMedCrossRefGoogle Scholar
  60. 60.
    Pszota HM, Kugler RK, Szigeti G. Fibrinopeptide-A as thrombotic risk marker in diabetic and atherosclerotic coronary vasculopathy. J Med 1992;23:93–100.PubMedGoogle Scholar
  61. 61.
    Morishita E, Asakura H, Jokaji H, et al. Hypercoagulability and high lipoprotein (a) levels in patients with type II diabetes mellitus. Atherosclerosis 1996;120:7–14.PubMedCrossRefGoogle Scholar
  62. 62.
    Myrup B, Rossing P, Jensen T, Gram J, Kluft C, Jespersen J. Procoagulant activity and intimal dysfunction in IDDM. Diabetologia 1995;38:73–78.PubMedCrossRefGoogle Scholar
  63. 63.
    Kannel WB, D’Agostino RB, Wilson PW, Belanger AJ, Gagnon DR. Diabetes, fibrinogen, and risk of cardiovascular disease: the Framingham experience. Am Heart J 1990;120:672–676.PubMedCrossRefGoogle Scholar
  64. 64.
    Lufkin EG, Fass DN, O’Fallon WM, Bowie EJW. Increased von Willebrand factor in diabetes mellitus. Metabolism 1979;28:63–66.PubMedCrossRefGoogle Scholar
  65. 65.
    Kannel WB, Wolf PA, Wilson PWF, D’Agostino RB. Fibrinogen and risk of cardiovasclarisease. JAMA 1987;258:1183–1186.PubMedCrossRefGoogle Scholar
  66. 66.
    Knobl P, Schernthaner G, Schnack C, et al. Haemostatic abnormalities persist despite glycaemic improvement by insulin therapy in lean type 2 diabetic patients. Thromb Haemost 1994;71:692–697.PubMedGoogle Scholar
  67. 67.
    Eliasson M, Roder ME, Dinesen B, Evrin PE, Lindahl B. Proinsulin, intact insulin, and fibrinolytic variables and fibrinogen in healthy subjects. Diabetes Care 1997;20:1252–1255.PubMedCrossRefGoogle Scholar
  68. 68.
    Warram JH, Martin BC, Krolewski AS, Soeldner JS, Kahn CR. Slow glucose removal rate and hyperinsulinemia precede the development of type II diabetes in the offspring of diabetic parents. Ann Intern Med 1990;113:909–915.PubMedCrossRefGoogle Scholar
  69. 69.
    Ward WK, LaCava EC, Paquette TL, Beard JC, Wallum BJ, Porte D. Disproportionate elevation of immunoreactive proinsulin in type 2 (non-insulindependent) diabetes mellitus and in experimental insulin resistance. Diabetologia 1987;30:698–702.PubMedCrossRefGoogle Scholar
  70. Ward WK, LaCava EC, Paquette TL, Beard JC, Wallum BJ, Porte D. Disproportionate elevation of immunoreactive proinsulin in type 2 (non-insulindependent) diabetes mellitus and in experimental insulin resistance. Diabetologia 1987;30:698–702.Google Scholar
  71. 70.
    Nagi DK, Hendra TJ, Ryle AJ, et al. 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.PubMedCrossRefGoogle Scholar
  72. 71.
    Marongiu F, Mascia F, Mameli G, Cirillo R, Balestrieri A. Prothromgin fragment F 1+ 2 levels are high in NIDDM patients independently of the Hb Al c. Thromb Haemost 1995;74:805–806.PubMedGoogle Scholar
  73. 72.
    Mansfield MW, Heywood DM, Grant PJ. Circulating levels of factor VII, fibrinogen, and von Willebrand factor and features of insulin resistance in firstdegree relatives of patients with NIDDM. Circulation 1996;94:2171–2176.PubMedCrossRefGoogle Scholar
  74. 73.
    Jude B, Watel A, Fontaine O, Cosson A. Distinctive features of procoagulant reponse of monocytes from diabetic patients. Haemostasis 1989;19:95–73.Google Scholar
  75. 74.
    Ceriello A, Russo PD, Zucotti C, et al. Decreased antithrombin III activity in diabetes may be due to non-enzymatic glycosylation: a preliminary report. Thromb Haemost 1983;50:633–634.PubMedGoogle Scholar
  76. 75.
    Brownlee M, Vlassara H, Cerami A. Inhibition of heparin-catalyzed human antithrombin III activity by nonenzymatic glycosylation. Diabetes 1984;33:532–535.PubMedCrossRefGoogle Scholar
  77. 76.
    Ceriello A, Giugliano D, Quatraro A, et al. Daily rapid blood glucose variations may condition antithrombin III biologic activity but not its plasma concentration in insulin-dependent diabetes: a possible role for labile on-enzymatic glycation. Diabetes Metab 1987;13:16–19.Google Scholar
  78. 77.
    Ceriello A, Quatraro A, Dello Russo P, et al. Protein C deficiency in insulin dependent diabetes: a hyperglycemia-related phenomenon. Thromb Haemost 1990;65:104–107.Google Scholar
  79. 78.
    The Diabetes Control and Complications Trial Research Group. The effect of intensive treatment of diabetes on the development and progression of longterm complications in insulin-dependent diabetes mellitus. N Engl J Med 1993;329:977–986.CrossRefGoogle Scholar
  80. 79.
    Auwerx J, Bouillon R, Collen D, Geboers J. Tissuetype plasminogen activator antigen and plasminogen activator inhibitor in diabetes mellitus. Arteriosclerosis 1988;8:68–72.PubMedCrossRefGoogle Scholar
  81. 80.
    McGill JB, Schneider DJ, Arfken CL, Lucore CL, Sobel BE. Factors responsible for impaired fibrinolysis in obese subjects and NIDDM patients. Diabetes 1994;43:104–109.PubMedCrossRefGoogle Scholar
  82. Vague P, JuhanVague I, Aillaud MF, et al. 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.CrossRefGoogle Scholar
  83. 82.
    Juhan-Vague I, Vague P, Alessi MC, et al. Relationships between plasma insulin, triglyceride, body mass index, and plasminogen activator inhibitor 1. Diabetes Metab 1987;13:331.Google Scholar
  84. 83.
    Keber I, Keber D. Increased plasminogen activator inhibitor activity in survivors of myocardial infarction is associated with metabolic risk factors of atherosclerosis. Haemostas 1992;22:187.Google Scholar
  85. 84.
    Nordt TK, Schneider DJ, Sobel BE. Augmentation of the synthesis of plasminogen activator inhibitor type- 1 by precursors of insulin: a potential risk factor for vascular disease. Circulation 1994;89:321–330.PubMedCrossRefGoogle Scholar
  86. 85.
    Calles-Escandon J, Mirza S, Sobel BE, Schneider DJ. Induction of hyperinsulinemia combined with hyperglycemia and hypertriglyceridemia increases plasminogen activator inhibitor type-1 (PAI-1) in blood in normal human subjects. Diabetes 1998;47:290–293.PubMedCrossRefGoogle Scholar
  87. 86.
    Ehrmann DA, Schneider, DJ, Sobel BE, et al. Troglitazone improves defects in insulin action, insulin secretion, ovarian steroidogenesis, and fibrinolysis in women with polycystic ovary syndrome. J Clin Endocrinol Metab 1997;82:2108–2116.PubMedCrossRefGoogle Scholar
  88. 87.
    Jansson JH, Johansson B, Boman K, Nilsson TK. Hypo-fibrinolysis in patients with hypertension and elevated cholesterol. J Intern Med 1991;229:309–316.PubMedCrossRefGoogle Scholar
  89. 88.
    Sampson M, Kong C, Patel A, Unwin R, Jacobs HS. Ambulatory blood pressure profiles and plasminogen activator inhibitor (PAI-1) activity in lean women with and without the polycytic ovary syndrome. Clin Endocrinol 1996;45:623–i29.CrossRefGoogle Scholar
  90. 89.
    Velazquez EM, Mendoza SG, Wang P, Glueck CJ. Metformin therapy is associated with a decrease in plasma plasminogen activator inhibitor-1, lipoprotein (a), and immunoreactive insulin levels in patients with the polycystic ovary syndrome. Metab Clin Exp 1997;46:454–457.PubMedCrossRefGoogle Scholar
  91. 90.
    Farrehi PM, Ozaki CK, Carmeliet P, Fay WP. Regulation of arterial thrombolysis by plasminogen activator inhibitor-1 in mice. Circulation 1998;97:1002–1008.PubMedCrossRefGoogle Scholar
  92. 91.
    Schneider DJ, Sobel BE. Synergistic augmentation of expression of PAI-1 induced by insulin, VLDL, and fatty acids. Coron Artery Dis 1996;7:813–817.PubMedCrossRefGoogle Scholar
  93. 92.
    Nordt TK, Klassen KJ, Schneider DJ, Sobel BE. 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.PubMedCrossRefGoogle Scholar
  94. 93.
    Chen YQ, Su M, Walia RR, Hao Q, Covington JW, Vaughan DE. Spl sites mediate activation of the plasminogen activaor inhibitor-1 promoter by glucose in vascular smooth muscle cells. J Biol Chem 1998;273:8225–8231.PubMedCrossRefGoogle Scholar
  95. 94.
    Samad F, Loskutoff DJ. Tissue distribution and regulation of plasminogen activator inhibitor-1 in obese mice. Mol Med 1996;2:568–582.PubMedGoogle Scholar
  96. 95.
    Lundgren CH, Sawa H, Brown SL, Nordt T, Sobel BE, Fujii S. Elaboration of type-1 plasminogen activator inhibitor from adipocytes: a potential pathogenetic link between obesity and cardiovascular disease. Circulation 1996;93:106–110.PubMedCrossRefGoogle Scholar
  97. 96.
    Calles-Escandon J, Ballor D, Harvey-Berino J, Ades P, Tracy R, Sobel BE. Amelioration of the inhibition of fibrinolysis in obese elderly subjects by moderate caloric restriction. Am J Clin Nutr 1996;64: 7–11.PubMedGoogle Scholar
  98. 97.
    Schneider DJ, Absher PM, Ricci MA. The dependence of augmentation of arterial endothelial cell expression of plasminogen activator inhibitor type 1 by insulin on soluble factors released from vascular smooth muscle cells. Circulation 1997;96:2868–2876.PubMedCrossRefGoogle Scholar
  99. 98.
    Pandolfi A, Iacoviello L, Capani F, Vitalonna E, Donati MB, Consoli A. Glucose and insulin independently reduce the fibrinolytic potential of human vascular smooth muscle cells in culture. Diabetologia 1996;39:1425–1431.PubMedCrossRefGoogle Scholar
  100. 99.
    Eliasson M, Asplund K, Evrin PE. Regular leisure time physical activity predicts high activity of tissue plamsinogen activator: the northern Sweden MONICA study. Int J Epidemiol 1996;25:1182–1188.PubMedCrossRefGoogle Scholar
  101. 100.
    Nordt TK, Kornas K, Peter K, et al. Attentuation by gemfibrozil of expression of plasminogen activator inhibitor type 1 induced by insulin and its precursors. Circulation 1997;95:677–683.PubMedCrossRefGoogle Scholar
  102. 101.
    Broijersen 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 Thrombs Vasc Biol 1996;16:511–516.CrossRefGoogle Scholar
  103. 102.
    Asplund-Carlson A. Effects of gemfibrozil therapy on glucose tolerance, insulin sensitivity and plasma plasminogen activator inhibitor activity in hypertriglyceridemia. J Cardiovasc Risk 1996;3:385–390.PubMedCrossRefGoogle Scholar
  104. 103.
    Rosenson RS, Tangney CC. Antiatherothrombotic properties of statins. Implications for cardiovascular event reduction. JAMA 1998;279:1643–1650.PubMedCrossRefGoogle Scholar
  105. 104.
    Libby P. Molecular bases of the acute coronary syndromes. Circulation 1995;91:2844–2850.PubMedCrossRefGoogle Scholar
  106. 105.
    Lang IM, Moser KM, Schleef RR. Elevated expression of urokinase-like plasminogen activator and plasminogen activator inhibitor type 1 during the vascular remodeling associated with pulmonary thromboembolism. Arterioscler Thromb Vasc Biol 1998;18:808–815.PubMedCrossRefGoogle Scholar
  107. 106.
    Schneider DJ, Ricci MA, Taatjes DJ, et al. Changes in arterial expression of fibrinolytic system proteins in atherogenesis. Arterioscler Thromb Vasc Biol 1997;17:3294–3301.PubMedCrossRefGoogle Scholar
  108. 107.
    Carmeliet P, Moons L, Lijnen R, et al. Inhibitory role of plasminogen inhibitor-1 in arterial wound healing and neointimal formation: a gene targeting and gene transfer study in mice. Circulation 1997;96: 3181–3191.CrossRefGoogle Scholar
  109. 108.
    Sobel BE, Woodcock-Mitchell J, Schneider DJ, Holt RE, Marutsuka K, Gold H. Increased plasminogen activator inhibitor type-1 in coronary artery atherectomy specimens from type 2 diabetic compared with nondiabetic patients: a potential factor predisposing to thrombosis and its persistence. Circulation 1998;97:2213–2221.PubMedCrossRefGoogle Scholar
  110. 109.
    Sobel BE. Potentiation of vasculopathy by insulin: implications from an NHLBI Clinical Alert. Circulation 1996;93:1613–1615.PubMedCrossRefGoogle Scholar
  111. 110.
    Carrozza JP, Kuntz RE, Fishman RF, Baim DS. Restenosis after arterial injury caused by coronary stenting in patients with diabetes mellitus. Ann Intern Med 1993;118:344–349.PubMedCrossRefGoogle Scholar
  112. 111.
    Minamikawa J, Tanaka S, Yamauchi M, Inoue D, Koshiyama H. Potent inhibitory effect of troglitazone on carotid arterial wall thickness in type 2 diabetes. J Clin Endocrinol Metab 1998;83:1818–1820.PubMedCrossRefGoogle Scholar
  113. 112.
    Otterstad JE, Hexeberg E, Holme I, Hjermann I. Cholesterol lowering therapy after myocardial infarction. Consequences of the CARE study. Tidsskr Nor Laegeforen 1997;117:2341–2344.PubMedGoogle Scholar
  114. 113.
    Colwell JA. Editorial: Elevated plasma homocysteine and diabetic vascular disease. Diabetes Care 1997;20:1805–1806.PubMedGoogle Scholar
  115. 114.
    Giugiano D, Ceriello A, Paolisso G. Oxidative stress and diabetic vascular complications. Diabetes Care 1996;19:257–267.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2001

Authors and Affiliations

  • David J. Schneider
  • Burton E. Sobel

There are no affiliations available

Personalised recommendations