Download PDF
Thromb Haemost 2000; 83(02): 304-308
DOI: 10.1055/s-0037-1613803
Rapid Communication
Schattauer GmbH

Role of Gender and Genetic Variance in Plasminogen Activator Inhibitor-1 Secretion from Human Adipose Tissue

Vanessa Van Harmelen
1   From the Department of Medicine and Research Center, Huddinge University Hospital, Karolinska Institute, Stockholm, Sweden
,
Hans Wahrenberg
1   From the Department of Medicine and Research Center, Huddinge University Hospital, Karolinska Institute, Stockholm, Sweden
,
Per Eriksson
2   Arteriosclerosis Research Unit, King Gustaf V Research Institute, Karolinska Institute, Stockholm, Sweden
,
Peter Arner
1   From the Department of Medicine and Research Center, Huddinge University Hospital, Karolinska Institute, Stockholm, Sweden
› Author Affiliations
Further Information

Publication History

Received 07 April 1999

Accepted after resubmission 02 September 1999

Publication Date:
11 December 2017 (online)

    Permissions and Reprints

Summary

Gender and the 4G/5G polymorphism in the plasminogen activator inhibitor 1 (PAI-1) gene are believed to play a role in the regulation of plasma PAI-1 activity. Adipose tissue has been found to be an important source of PAI-1. The possible influence of gender and the 4G/5G polymorphism in the PAI-1 gene on PAI-1 secretion from abdominal subcutaneous adipose tissue was investigated in 59 women and 32 men. The subjects were apparantly healthy, although they differed markedly inter-individually in body mass index (21-53 kg/m2). The 4G/5G polymorphism did not influence the adipose secretion rate of PAI-1 or plasma PAI-1 activity. There was no gender difference in the adipose secretion of PAI-1. In multiple regression, including body mass index (BMI), waist-to-hip ratio (WHR), plasma insulin and plasma triglycerides as the independent and adipose PAI-1 secretion as the dependent variable, only BMI and plasma triglycerides correlated independently with adipose PAI-1 secretion (r = 0.54, p <0.05; r = 0.51, p <0.05, respectively). Men had a two times higher plasma PAI-1 activity than women (p <0.05). This gender difference was mainly due to gender differences in WHR. In multiple regression analysis, BMI and WHR were identified to be independently correlated with plasma PAI-1 activity (r = 0.60, p <0.05; r = 0.52, p = 0.01, respectively). In conclusion, neither gender nor the 4G/5G polymorphism in the PAI-1 gene are associated with secretion of PAI-1 from abdominal subcutaneous adipose tissue.

 

  • References

  • 1 Wiman B, Hamsten A. The fibrinolytic enzyme system and its role in the etiology of thrombotic disease. Semin Thromb Haemost 1990; 26: 207-16.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 2 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: 1557-63.
    CrossrefPubMedGoogle Scholar
  • 3 Auwerx J, Bouillon R, Collen D, Geboers J. Tissue-type plasminogen activator antigen and plasminogen activator inhibitor in diabetes mellitus. Arteriosclerosis 1988; 08: 68-72.
    CrossrefPubMedGoogle Scholar
  • 4 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: 2503.
    PubMedGoogle Scholar
  • 5 Hamsten A, de Faire U, Walldius G, Dahlen G, Szamosi A, Landou C, Blombäck M, Wiman B. Plasminogen activator inhibitor in plasma: risk factor for recurrent myocardial infarction. Lancet 1987; 02: 3-9.
    PubMedGoogle Scholar
  • 6 Wiman B, Hamsten A. Impaired fibrinolysis and risk of thromboembolism. Prog Cardiovasc Dis 1991; 34: 179-92.
    CrossrefPubMedGoogle Scholar
  • 7 Samad F, Yamamoto K, Loskutoff DJ. Distribution and regulation of plasminogen activator inhibitor-1 in murine adipose tissue in vivo Induction by tumor necrosis factor-alpha and lipopolysaccharide. J Clin Invest 1996; 97: 37-46.
    CrossrefPubMedGoogle Scholar
  • 8 Alessi MC, Peiretti F, Morange P, Henry M, Nalbone G, Juhan-Vague I. Production of plasminogen activator inhibitor 1 by human adipose tissue: Possible link between visceral fat accumulation and vascular disease. Diabetes 1997; 46: 860-7.
    CrossrefPubMedGoogle Scholar
  • 9 Eriksson P, Reynisdottir S, Lönnqvist F, Stemme V, Hamsten A, Arner P. Adipose tissue secretion of plasminogen activator inhibitor-1 in non-obese and obese individuals. Diabetologia 1998; 41: 65-71.
    CrossrefPubMedGoogle Scholar
  • 10 Lerner DJ, Kannel WB. Patterns of coronary heart disease morbidity and mortality in the sexes: a 26-year follow-up of the Framingham population. Am Heart J 1983; 11: 383-90.
    PubMedGoogle Scholar
  • 11 Stegnar M, Pentek M. Fibrinolytic response to venous occlusion in healthy subjects: relationship to age, gender, body weight, blood lipids and insulin. Thrombosis Research 1993; 69: 81-92.
    CrossrefPubMedGoogle Scholar
  • 12 Toft I, Bonaa KH, Ingebretsen OC, Nordoy A, Birkeland K, Jenssen T. Gender differences in the relationships between plasma plasminogen activator inhibitor-1 activity and factors linked to the insulin resistance syndrome in essential hypertension. Arterioscler Thromb Vasc Biol 1997; 17: 553-9.
    CrossrefPubMedGoogle Scholar
  • 13 Ossei-Gerning N, Mansfield MW, Stickland MH, Wilson IJ, Grant PJ. Plasminogen activator inhibitor-1 promoter 4G/5G genotype and plasma levels in relation to a history of myocardial infarction in patients characterized by coronary angiography. Arterioscler Thromb Vasc Biol 1997; 17: 33-7.
    CrossrefPubMedGoogle Scholar
  • 14 Krishnamurti C, Tang DB, Barr CF, Alving BM. Plasminogen activator and plasminogen activator inhibitor activities in a reference population. Am J Clin Pathol 1988; 89: 747-52.
    CrossrefPubMedGoogle Scholar
  • 15 Lacroix KA, Bean C, Box L, Wagner K. A study of the fibrinolytic response in healthy men and women following a brief exposure to venous occlusion. Thromb Res 1996; 81: 133-43.
    CrossrefPubMedGoogle Scholar
  • 16 Sundell IB, Nilsson TK, Ranby M, Hallmans G, Hellsten G. Fibrinolytic variables are related to age, sex, blood pressure, and body build measurements: a cross-sectional study in Norsjo, Sweden. J Clin Epidemiol 1989; 42: 712-23.
    PubMedGoogle Scholar
  • 17 Dawson S, Hamsten A, Wiman B, Henney A, Humphries SE. Genetic variation at the plasminogen activator inhibitor-1 locus is associated with altered levels of plasma plasminogen activator inhibitor-1 activity. Arterioscler Thromb 1991; 11: 183-90.
    CrossrefPubMedGoogle Scholar
  • 18 Klinger KW, Winqvist R, Riccio A, Andreasen PA, Sartorio R, Nielsen LS, Stuart N, Stanislovitis P, Watkins P, Douglas R, Grzeschil KH, Alitalo K. Plasminogen activator inhibitor type 1 gene is located at region q21.3-q22 of chromosome 7 and genetically linked with cystic fibrosis. Proc Natl Acad Sci USA 1991; 84: 8548-52.
    PubMedGoogle Scholar
  • 19 Dawson SJ, Wiman B, Hamsten A, Green F, Humphries S, Henney AM. The two allele sequences of a common polymorphism in the promoter of the plasminogen activator inhibitor-1 (PAI-1) gene respond differently to interleukin-1 in HepG2 cells. J Biol Chem 1993; 268: 10739-45.
    PubMedGoogle Scholar
  • 20 Eriksson P, Kallin B, van’t FMHooft, Båvenholm P, Hamsten A. Allelespecific increase in basal transcription of the plasminogen activator inhibitor-1 gene is associated with myocardial infarction. Proc Natl Acad Sci USA 1995; 92: 1851-5.
    CrossrefPubMedGoogle Scholar
  • 21 Ye S, Green FR, Scarabin PY, Nicaud V, Bara L, Dawson SJ, Humphries SE, Evans A, Luc G, Cambou JP, Arveiler D, Henney AM, Cambien F. The 4G/4G genetic polymorphism in the promoter of the plasminogen activator-1 (PAI-1) gene is associated with differences in plasma PAI-1 activity but not with risk of myocardial infarction in the ECTIM study. Thromb Haemost 1995; 74: 837-41.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 22 Panahloo A, Mohamed-Ali V, Lane A, Green F, Humphries SE, Yudkin JS. Determinants of plasminogen activator inhibitor-1 activity in treated NIDDM and its relation to a polymorphism in the plasminogen activator-1 gene. Diabetes 1995; 44: 37-42.
    CrossrefPubMedGoogle Scholar
  • 23 Arner P, Arner O, Ostman J. The effect of local anaesthetic agents on lipolysis by human adipose tissue. Life Sci 1973; 13: 161-9.
    CrossrefPubMedGoogle Scholar
  • 24 Rodbell M. Metabolism of isolated fat cells. J Biol Chem 1964; 239: 375-80.
    PubMedGoogle Scholar
  • 25 Henry M, Chomiki N, Scarabin PY, Alessi MC, Peiseffi F, Arveiler D, Ferrieres J, Evans A, Amoyel P, Poirier O, Cambien F, Juhan-Vague I. Five frequent polymorphisms of the PAI-1 gene: lack of association between genotypes, PAI-1 activity and triglyceride levels in a healthy population. Arterioscler Thromb Vasc Biol 1997; 17: 851-8.
    CrossrefPubMedGoogle Scholar
  • 26 Eriksson P, Nilsson L, Karpe F, Hamsten A. Very-Low-Density lipoprotein response element in the promoter region of the human plasminogen activator inhibitor-1 gene implicated in the impaired fibrinolysis of hypertriglyceridemia. Arterioscler Thromb Vasc Biol 1998; 18: 20-6.
    CrossrefPubMedGoogle Scholar
  • 27 Landin K, Stigendal L, Eriksson E, Krorkiewski M, Risberg B, Tengborn L, Smith U. Abdominal obesity is associated with an impaired fibrinolytic activity and elevated plasminogen activator inhibitor-1. Metabolism 1990; 15: 619-22.
    PubMedGoogle Scholar
  • 28 De Pergola G, De Mitrio V, Sciaraffia M, Pannacciulli N, Minenna A, Giorgino F, Petronelli M, Laudadio E, Giorgino R. Lower androgenicity is associated with higher plasma levels of prothrombotic factors irrespective of age, obesity, body fat distribution, and related metabolic parameters in men. Metabolism 1997; 46: 1287-93.
    CrossrefPubMedGoogle Scholar
  • 29 Canfield AE, Schor AM, Loskutoff DJ, Schor SL, Grant ME. Plasminogen activator inhibitor 1 is a major biosynthetic product of retinal microvascular endothelial cells and pericytes in culture. Biochem J 1989; 259: 529-35.
    CrossrefPubMedGoogle Scholar
  • 30 Sprengers ED, Verheijen JH, Van Hinsbergh VWM, Emeis JJ. Evidence for the presence of two different fibrinolytic inhibitors in human endothelial cell conditioned medium. Biochim Biophys Acta 1984; 801: 163-70.
    CrossrefPubMedGoogle Scholar