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Relationships of PAI-1 levels to central obesity and liver steatosis in a sample of adult male population in southern Italy

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Abstract

To analyse the relationship of PAI-1 plasma levels to echographically determined liver steatosis and cardiometabolic risk factors in a randomly selected sample of 254 adult male participants of the Olivetti Heart Study. Accounting for age and ongoing pharmacological treatment, PAI-1 levels were directly (P < 0.005) associated with body mass index (BMI), waist circumference (WC), serum triglyceride (TG), total cholesterol, insulin, homeostasis model assessment index, gamma-glutamyl transpeptidase and peritoneal fat. At multiple linear regression (MLR) analysis, measures of adiposity and TG exerted significant and quantitatively similar effects on PAI-1 levels. A progressive rise in PAI-1 level was detected with increasing degree of steatosis. A stepwise MLR model was used to evaluate the relative power of cardiometabolic risk factors and liver steatosis on PAI-1 levels. Adjusting for alcohol intake, BMI, WC and peritoneal fat were alternatively included in the model with other variables found to be significantly associated with plasma PAI-1 level. Liver steatosis, serum TG and various indexes of adiposity each had a significant independent impact on PAI-1 plasma level and explained overall 23% of its variability. Abdominal fat, liver steatosis and serum TG levels were significant and independent determinants of PAI-1 plasma level in an unselected sample of adult male population upon adjustment for age and therapy.

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References

  1. Loskutoff DJ, Samad F (1998) The adipocyte and hemostatic balance in obesity: studies of PAI-1. Arterioscler Thromb Vasc Biol 18:1–6

    PubMed  CAS  Google Scholar 

  2. Dellas C, Loskutoff DJ (2005) Historical analysis of PAI-1 from its discovery to its potential role in cell motility and disease. Thromb Haemost 93:631–640

    PubMed  CAS  Google Scholar 

  3. Kruithof EKO (1988) Plasminogen activator inhibitor type 1: biochemical, biological and clinical aspects. Fibrinolysis 2:59–70

    CAS  Google Scholar 

  4. Samad F, Loskutoff DJ (1996) Tissue distribution and regulation of plasminogen activator inhibitor-1 in obese mice. Mol Med 2:568–582

    PubMed  CAS  Google Scholar 

  5. Mertens I, Van Gaal LF (2005) Visceral fat as a determinant of fibrinolysis and hemostasis. Semin Vasc Med 5:48–55

    Article  PubMed  Google Scholar 

  6. Schafer K, Fujisawa K, Konstantinides S, Loskutoff DJ (2001) Disruption of the plasminogen activator inhibitor 1 gene reduces the adiposity and improves the metabolic profile of genetically obese and diabetic ob/ob mice. FASEB J 15:1840–1842

    PubMed  CAS  Google Scholar 

  7. Vaughan DE (2005) PAI-1 and atherothrombosis. J Thromb Haemost 3:1879–1883

    Article  PubMed  CAS  Google Scholar 

  8. Margaglione M, Di Minno G, Grandone E et al (1994) Abnormally high circulation levels of tissue plasminogen activator and plasminogen activator inhibitor-1 in patients with a history of ischemic stroke. Arterioscler Thromb 14:1741–1745

    PubMed  CAS  Google Scholar 

  9. Thögersen AM, Jansson JH, Boman K et al (1998) High plasminogen activator inhibitor and tissue plasminogen activator levels in plasma precede a first acute myocardial infarction in both men and women. Evidence for the fibrinolytic system as an independent primary risk factor. Circulation 98:2241–2247

    PubMed  Google Scholar 

  10. Hamsten A, de Faire U, Walldius G et al (1987) Plasminogen activator inhibitor in plasma: risk factor for recurrent myocardial infarction. Lancet 2:3–9

    Article  PubMed  CAS  Google Scholar 

  11. Juhan-Vague I, Pyke SD, Alessi MC et al (1996) Fibrinolytic factors and the risk of myocardial infarction or sudden death in patients with angina pectoris: ECAT Study Group: European Concerted Action on Thrombosis and Disabilities. Circulation 94:2057–2063

    PubMed  CAS  Google Scholar 

  12. Juhan-Vague I, Alessi MC, Mavri A, Morange PE (2003) Plasminogen activator inhibitor-1, inflammation, obesity, insulin resistance and vascular risk. J Thromb Haemost 1:1575–1579

    Article  PubMed  CAS  Google Scholar 

  13. Appel SJ, Harrell JS, Davenport ML (2005) Central obesity, the metabolic syndrome, and plasminogen activator inhibitor-1 in young adults. J Am Acad Nurse Pract 17:535–541

    Article  PubMed  Google Scholar 

  14. Juhan-Vague I, Alessi MC, Vague P (1991) Increased plasma plasminogen activator inhibitor-1 levels. A possible link between insulin resistance and atherothrombosis. Diabetologia 34:457–462

    Article  PubMed  CAS  Google Scholar 

  15. Mertens I, Verrijken A, Michiels JJ et al (2006) Among inflammation and coagulation markers, PAI-1 is a true component of the metabolic syndrome. Int J Obes (Lond) 30:1308–1314

    Article  CAS  Google Scholar 

  16. Cigolini M, Targher G, Agostino G et al (1996) Liver steatosis and its relation to plasma haemostatic factors in apparently healthy men—role of the metabolic syndrome. Thromb Haemost 76:69–73

    PubMed  CAS  Google Scholar 

  17. Bruckert E, Ankri A, Giral P, Turpin G (1994) Relation between plasminogen activator inhibitor-1 and hepatic enzyme concentrations in hyperlipidemic patients. Thromb Haemost 72:434–437

    PubMed  CAS  Google Scholar 

  18. Akahoshi M, Amasaki Y, Soda M et al (2001) Correlation between fatty liver and coronary risk factors: a population study of elderly men and women in Nagasaki, Japan. Hypertens Res 24:337–343

    Article  PubMed  CAS  Google Scholar 

  19. Osono Y, Nakajima K, Hata Y (1995) Hypertriglyceridemia and fatty liver: clinical diagnosis of fatty liver and lipoprotein profiles in hypertriglyceridemic patients with fatty liver. J Atheroscler Thromb 2:S47–S52

    PubMed  CAS  Google Scholar 

  20. Strazzullo P, Barba G, Cappuccio FP et al (2001) Altered renal sodium handling in men with abdominal adiposity. A link to hypertension. J Hypertens 19:2157–2164

    Article  PubMed  CAS  Google Scholar 

  21. Matthews DR, Hosker JP, Rudenski AS et al (1985) Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 28:412–419

    Article  PubMed  CAS  Google Scholar 

  22. Bonora E, Kiechl S, Willeit J et al (1998) Prevalence of insulin resistance in metabolic disorders: the Bruneck Study. Diabetes 47:1643–1649

    Article  PubMed  CAS  Google Scholar 

  23. Ribeiro-Filho FF, Faria AN, Azjen S et al (2003) Methods of estimation of visceral fat: advantages of ultrasonography. Obes Res 11:1488–1494

    Article  PubMed  Google Scholar 

  24. Strauss S, Gavish E, Gottlieb P, Katsnelson L (2007) Interobserver and intraobserver variability in the sonographic assessment of fatty liver. AJR Am J Roentgenol 189:W320–W323

    Article  PubMed  Google Scholar 

  25. Adams LA, Angulo P (2005) Recent concepts in non-alcoholic fatty liver disease. Diabet Med 22:1129–1133

    Article  PubMed  CAS  Google Scholar 

  26. Joseph AE, Saverymuttu SH, al-Sam S et al (1991) Comparison of liver histology with ultrasonography in assessing diffuse parenchymal liver disease. Clin Radiol 43:26–31

    Article  PubMed  CAS  Google Scholar 

  27. Palmentieri B, de Sio I, La Mura V et al (2006) The role of bright liver echo pattern on ultrasound B-mode examination in the diagnosis of liver steatosis. Dig Liver Dis 38:485–489

    Article  PubMed  CAS  Google Scholar 

  28. Grundy SM, Cleeman JI, Daniels SR et al (2005) Diagnosis and management of the metabolic syndrome: an American Heart Association/National Heart, Lung, and Blood Institute Scientific Statement. Circulation 112:2735–2752

    Article  PubMed  Google Scholar 

  29. Alessi MC, Bastelica D, Mavri A et al (2003) Plasma PAI-1 levels are more strongly related to liver steatosis than to adipose tissue accumulation. Arterioscler Thromb Vasc Biol 23:1262–1268

    Article  PubMed  CAS  Google Scholar 

  30. Targher G, Bertolini L, Scala L et al (2005) Non-alcoholic hepatic steatosis and its relation to increased plasma biomarkers of inflammation and endothelial dysfunction in non-diabetic men. Role of visceral adipose tissue. Diabet Med 22:1354–1358

    Article  PubMed  CAS  Google Scholar 

  31. Fan JG, Chen LH, Xu ZJ, Zeng MD (2001) Overexpression of hepatic plasminogen activator inhibitor type 1 mRNA in rabbits with fatty liver. World J Gastroenterol 7:710–712

    PubMed  CAS  Google Scholar 

  32. de Larrañaga G, Wingeyer SP, Graffigna M et al (2008) Plasma plasminogen activator inhibitor-1 levels and nonalcoholic fatty liver in individuals with features of metabolic syndrome. Clin Appl Thromb Hemost 14:319–324

    Article  PubMed  Google Scholar 

  33. Nilsson L, Gafvels M, Musakka L et al (1999) VLDL activation of plasminogen activator inhibitor-1 (PAI-1) expression: involvement of the VLDL receptor. J Lipid Res 40:913–919

    PubMed  CAS  Google Scholar 

  34. Olufadi R, Byrne CD (2006) Effects of VLDL and remnant particles on platelets. Pathophysiol Haemost Thromb 35:281–291

    Article  PubMed  CAS  Google Scholar 

  35. McCuskey RS, Ito Y, Robertson GR et al (2004) Hepatic microvascular dysfunction during evolution of dietary steatohepatitis in mice. Hepatology 40:386–393

    Article  PubMed  Google Scholar 

  36. Li Z, Yang S, Lin H et al (2003) Probiotics and antibodies to TNF inhibit inflammatory activity and improve nonalcoholic fatty liver disease. Hepatology 37:343–350

    Article  PubMed  CAS  Google Scholar 

  37. Yin M, Wheeler MD, Kono H et al (1999) Essential role of tumor necrosis factor alpha in alcohol-induced liver injury in mice. Gastroenterology 117:942–952

    Article  PubMed  CAS  Google Scholar 

  38. Villanova N, Moscatiello S, Ramilli S et al (2005) Endothelial dysfunction and cardiovascular risk profile in nonalcoholic fatty liver disease. Hepatology 42:473–480

    Article  PubMed  Google Scholar 

  39. Jepsen P, Vilstrup H, Mellemkjaer L et al (2003) Prognosis of patients with a diagnosis of fatty liver—a registry-based cohort study. Hepatogastroenterology 50:2101–2104

    PubMed  Google Scholar 

  40. Volzke H, Robinson DM, Kleine V et al (2005) Hepatic steatosis is associated with an increased risk of carotid atherosclerosis. World J Gastroenterol 11:1848–1853

    PubMed  Google Scholar 

  41. Sieri S, Agudo A, Kesse E et al (2002) Patterns of alcohol consumption in 10 European countries participating in the European Prospective Investigation into Cancer and Nutrition (EPIC) project. Public Health Nutr 5(6B):1287–1296

    Article  PubMed  CAS  Google Scholar 

  42. Volpato S, Pahor M, Ferrucci L et al (2004) Relationship of alcohol intake with inflammatory markers and plasminogen activator inhibitor-1 in well-functioning older adults: the Health, Aging, and Body Composition study. Circulation 109:607–612

    Article  PubMed  CAS  Google Scholar 

  43. Mukamal KJ, Jadhav PP, D’Agostino RB et al (2001) Alcohol consumption and hemostatic factors: analysis of the Framingham Offspring cohort. Circulation 104:1367–1373

    Article  PubMed  CAS  Google Scholar 

  44. Sasaki A, Kurisu A, Ohno M, Ikeda Y (2001) Overweight/obesity, smoking, and heavy alcohol consumption are important determinants of plasma PAI-1 levels in healthy men. Am J Med Sci 322:19–23

    Article  PubMed  CAS  Google Scholar 

  45. Djousse L, Pankow JS, Arnett DK et al (2000) Alcohol consumption and plasminogen activator inhibitor type 1: the National Heart, Lung, and Blood Institute Family Heart Study. Am Heart J 139:704–709

    Article  PubMed  CAS  Google Scholar 

  46. Ishii M, Yoshioka Y, Ishida W et al (2005) Liver fat content measured by magnetic resonance spectroscopy at 3.0 tesla independently correlates with plasminogen activator inhibitor-1 and body mass index in type 2 diabetic subjects. Tohoku J Exp Med 206:23–30

    Article  PubMed  CAS  Google Scholar 

  47. Alessi MC, Lijnen HR, Bastelica D, Juhan-Vague I (2003) Adipose tissue and atherothrombosis. Pathophysiol Haemost Thromb 33:290–297

    Article  PubMed  Google Scholar 

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Conflict of interest statement

The authors declare that they have no conflict of interest related to the publication of this manuscript.

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Authors and Affiliations

  1. Department of Clinical and Experimental Medicine, “Federico II” University of Naples Medical School, Via S. Pansini, 5, 80131, Naples, Italy

    Antonio Barbato, Roberto Iacone, Giovanni Tarantino, Ornella Russo, Paolo Sorrentino, Sonia Avallone, Ferruccio Galletti & Pasquale Strazzullo

  2. Department of Preventive Medical Sciences, Federico II University, Naples, Italy

    Eduardo Farinaro & Elisabetta Della Valle

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  1. Antonio Barbato
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  2. Roberto Iacone
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  3. Giovanni Tarantino
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  10. Pasquale Strazzullo
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on behalf of The Olivetti Heart Study Research Group

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Correspondence to Pasquale Strazzullo.

Additional information

The Olivetti Heart Study Research Group: P. Strazzullo (coordinator), G. Barba, F. P. Cappuccio, E. Farinaro, F. Galletti, A. Siani.

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Barbato, A., Iacone, R., Tarantino, G. et al. Relationships of PAI-1 levels to central obesity and liver steatosis in a sample of adult male population in southern Italy. Intern Emerg Med 4, 315–323 (2009). https://doi.org/10.1007/s11739-009-0240-9

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  • DOI: https://doi.org/10.1007/s11739-009-0240-9

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