Download PDF
Thromb Haemost 1996; 76(03): 417-421
DOI: 10.1055/s-0038-1650593
Original Article
Schattauer GmbH Stuttgart

Plasminogen Activator Inhibitor 1 Is Elevated in the Children of Men with Premature Myocardial Infarction

Loukianos S Rallidis
Supported by the Department of Cardiology, Evangelismos Hospital, Athens, Greece
,
Ageliki A Megalou
2   Blood Transfusion Service, Evangelismos Hospital, Athens, Greece
,
Nikos H Papageorgakis
1   Biochemistry Laboratory, Evangelismos Hospital, Athens, Greece
,
Athanasios G Trikas
Supported by the Department of Cardiology, Evangelismos Hospital, Athens, Greece
,
Grammatiki I Chatzidimitriou
2   Blood Transfusion Service, Evangelismos Hospital, Athens, Greece
,
George K Tsitouris
Supported by the Department of Cardiology, Evangelismos Hospital, Athens, Greece
› Author Affiliations
Further Information

Publication History

Received 12 July 1995

Accepted after resubmission 13 May 1996

Publication Date:
10 July 2018 (online)

  PDF Download  Permissions and Reprints

Summary

To assess whether plasminogen activator inhibitor 1 (PAI-1) activity is elevated in the progeny of young coronary men, 193 young subjects were recruited and divided into two groups. Group A consisted of 104 children whose fathers had suffered a myocardial infarction before the age of 55 (“cases”). Eighty-nine young subjects matched for age, sex, body mass index (BMI) and smoking habits without familial history of coronary artery disease (CAD) served as controls (group B). Children with a family history of diabetes mellitus or hypertension were excluded from both groups. We measured PAI-1 activity, tissue-type plasminogen activator (t-PA) antigen, a2-antiplasmin, fibrinogen, lipids and apolipoproteins in both groups. PAI-1 activity levels were also determined in the men who suffered a premature myocardial infarction 4 months after their discharge. PAI-1 activity levels were higher in cases compared to controls (3.13 ± 1.9 vs 2.17 ± 1.9 U/ml, p = 0.0014). t-PA antigen and a2-antiplasmin did not differ significantly between the two groups, while fibrinogen, total cholesterol, low-den-sity lipoprotein cholesterol, apolipoprotein B and lipoprotein(a) were significantly higher in group A. PAI-1 was positively correlated with triglycerides (r = 0.22, p = 0.024), apolipoprotein B (r = 0.21, p = 0.039) and fibrinogen (r = 0.22, p = 0.029 ) in cases and with BMI in both cases (r = 0.37, p = 0.0003) and controls (r = 0.23, p = 0.044). In stepwise multiple regression analysis, only apolipoprotein B (p = 0.008) and BMI (p = 0.0014) were significant determinants of PAI-1 activity in cases. There was also a positive correlation between PAI-1 activity levels of the affected fathers and their children (r = 0.30, p = 0.01). The present data support the hypothesis that elevated PAI-1 levels in the offspring of men with premature myocardial infarction impair their fibrinolytic capacity contributing to their familial predisposition to CAD.

 

  • References

  • 1 Chmielwska J, Ranby M, Wiman B. Evidence for a rapid inhibitor to tissue plasminogen activator inhibitor in plasma. Thromb Res 1983; 31: 427-436
    CrossrefPubMedGoogle Scholar
  • 2 Chandler WL. A kinetic model of the circulatory regulation of tissue plasminogen activator. Thromb Haemost 1991; 66: 321-328
    Article in Thieme ConnectPubMedGoogle Scholar
  • 3 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; 2: 3-9
    PubMedGoogle Scholar
  • 4 Barbash GI, Hod H, Roth A, Miller HI, Rath S, Harzahav Y, Modan M, Zivelin A, Laniado S, Seligsohn U. 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
    CrossrefPubMedGoogle Scholar
  • 5 Levi M, Biemond BJ, Van Zonneveld AJ, Ten Cate JW, 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
    CrossrefPubMedGoogle Scholar
  • 6 Chomiki N, Henry M, Alessi MC, Anfosso F, Juhan-Vague I. Plasminogen activator inhibitor-1 expression in human liver and healthy or atherosclerotic vessel walls. Thromb Haemost 1994; 72: 44-53
    PubMedGoogle Scholar
  • 7 Lupu F, Bergonzelli GE, Heim DA, Cousin E, Genton CY, Bachmann F, Kruithof EKO. Localization and production of plasminogen activator inhibitor-1 in human healthy and atherosclerotic arteries. Arterioscler Thromb 1993; 13: 1090-1100
    CrossrefPubMedGoogle Scholar
  • 8 Holman RL, McGill Jr HC, Strong JP, Geer JC. The natural history of atherosclerosis. The early aortic lesions as seen in the middle of 20th century. Am J Pathol 1958; 34: 209-235
    PubMedGoogle Scholar
  • 9 Enos WF, Holmes RH, Beyer J. Coronary disease among United States soldiers killed in action in Korea: Preliminary report. JAMA 1953; 152: 1090-1093
    CrossrefPubMedGoogle Scholar
  • 10 Rissanen AM, Nikkila EA. Aggregation of coronary risk factors in families of men with fatal and non-fatal coronary heart disease. Br Heart J 1979; 42: 373-380
    CrossrefPubMedGoogle Scholar
  • 11 Ten Kate LP, Boman H, Daiger SP, Motulsky AG. Familial aggregation of coronary heart disease and its relation to known genetic risk factors. Am J Cardiol 1982; 50: 945-953
    CrossrefPubMedGoogle Scholar
  • 12 Clauss A. Gerinnungsphysiologische Schnellmethode zur Bestimmung des Fibrinogens. Acta Haematol 1957; 17: 237-246
    CrossrefPubMedGoogle Scholar
  • 13 Bara L, Nicaud V, Tiret L, Cambien F, Samama MM. Expression of a paternal history of premature myocardial infarction on fibrinogen, factor VIIC and PAI-1 in European offspring - The EARS Study. Thromb Haemost 1994; 71: 434-440
    Article in Thieme ConnectPubMedGoogle Scholar
  • 14 Paramo JA, Colucci M, Collen D, Van de Werf F. Plasminogen activator inhibitor in the blood of patients with coronary artery disease. Br Med J 1985; 291: 573-574
    CrossrefPubMedGoogle Scholar
  • 15 Olofsson BO, Dahlen G, Nilsson TK. 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
    CrossrefPubMedGoogle Scholar
  • 16 Huber K, Resch I, Stefenelli T, Lang I, Probst P, Kaindl F, Binder BR. Plasminogen activator inhibitor-1 levels in patients with chronic angina pectoris with or without angiographic evidence of coronary sclerosis. Thromb Haemost 1990; 63: 336-339
    Article in Thieme ConnectPubMedGoogle Scholar
  • 17 Thompson SG, Van De Loo JCW. ECAT Angina Pectoris Study. Baseline associations of haemostatic factors with extent of coronary arteriosclerosis and other coronary risk factors in 3000 patients with angina pectoris undergoing coronary angiography. Eur Heart J 1993; 14: 8-17
    PubMedGoogle Scholar
  • 18 Heinrich J, Schulte H, Schonfeld R, Kohler E, Assmann G. Association of variables of coagulation, fibrinolysis and acute-phase with atherosclerosis in coronary and peripheral arteries and those arteries supplying the brain. Thromb Haemost 1995; 73: 374-379
    Article in Thieme ConnectPubMedGoogle Scholar
  • 19 Klinger K, Winqvist R, Riccio A, Andreasen PA, Sartorio R, Nielson LS, Stuart N, Stanislovitis P, Watkins P, Douglas R. et al 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 1987; 84: 8548-8552
    CrossrefPubMedGoogle Scholar
  • 20 Dawson S, Hamsten A, Wiman B, Henney A, Humphries S. 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: 183-190
    CrossrefPubMedGoogle Scholar
  • 21 Eriksson P, Kallin B, van’t Hooft FM, Bavenholm P, Hamsten A. Allele-specific increase in basal transcription of the plasminogen-activator inhibitor 1 gene is associated with myocardial infarction. Proc Natl Acad Sci 1995; 92: 1851-1855
    CrossrefPubMedGoogle Scholar
  • 22 Salomaa V, Stinson V, Kark JD, Folsom AR, Davis CE, Wu KK. Association of fibrinolytic parameters with early atherosclerosis. The ARIC study. Circulation 1995; 91: 284-290
    PubMedGoogle Scholar
  • 23 Ross R. The process of atherogenesis - cellular and molecular interaction: from experimental animal models to humans. Diabetologia 1992; 35 (Suppl. 02) S34-S40
    CrossrefPubMedGoogle Scholar
  • 24 Emeis J, Kooistra T. Interleukin-1 and lipopolysaccharide induce a fast acting inhibitor of tissue-type plasminogen activator in vivo and in cultured endothelial cells. J Exp Med 1986; 163: 1260-1266
    CrossrefPubMedGoogle Scholar
  • 25 de Boer JP, Abbink JJ, Brouwer MC, Meijer C, Roem S, Voom GP, Lambers JWJ, van Mouric JA, Hack CE. PAI-1 synthesis in the human hepatoma cell line hep G2 is increased by cytokines - evidence that the liver contributes to acute phase behaviour of PAI-1. Thromb Haemost 1991; 65: 181-185
    Article in Thieme ConnectPubMedGoogle Scholar
  • 26 ECAT angina pectoris study: baseline associations of haemostatic factors with extent of coronary arteriosclerosis and other coronary risk factors in 3000 patients with angina pectoris undergoing coronary angiography. Eur H Journal 1993; 14: 8-17
    PubMedGoogle Scholar
  • 27 Ridker PM, Vaughan DE, Stampfer MJ, Manson JE, Hennekens CH. Endogenous tissue-type plasminogen activator and risk of myocardial infarction. Lancet 1993; 341: 1165-1168
    CrossrefPubMedGoogle Scholar
  • 28 Caron P, Bennet A, Camare R, Louvet JP, Boneu B, Sié P. Plasminogen activator inhibitor in plasma is related to testosterone in men. Metabolism 1989; 38: 1010-1015
    CrossrefPubMedGoogle Scholar
  • 29 Scarabin PY, Bonithon-Kopp C, Bara L, Guize L, Samama M. Relationship between plasminogen activator inhibitor activity and menopausal status. Fibrinolysis 1990; 4: 233-236
    PubMedGoogle Scholar
  • 30 Sizonenko PC. Endocrinology in preadolescents and adolescents. Part 1: hormonal changes during normal puberty. Am J Dis Child 1978; 132: 704-712
    CrossrefPubMedGoogle Scholar
  • 31 Juhan-Vague I, Vague P, Alessi MC, Badier C, Valadier J, Aillaud MF, Atlan C. Relationships between plasma insulin, triglyceride, body mass index and plasminogen activator inhibitor 1. Diab Metab 1987; 13: 331-336
    PubMedGoogle Scholar
  • 32 Mehta J, Mehta P, Lawson D, Saldeen T. Plasma tissue plasminogen activator inhibitor levels in coronary artery disease: correlation with age and serum triglyceride concentrations. J Am Coll Cardiol 1987; 9: 263-268
    CrossrefPubMedGoogle Scholar
  • 33 Gray RP, Mohamed-Ali V, Patterson DLH, Yudkin JS. Determinants of plasminogen activator inhibitor-1 activity in survivors of myocardial infarction. Thromb Haemost 1995; 73: 261-267
    Article in Thieme ConnectPubMedGoogle Scholar
  • 34 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 lipoproteins. Arteriosclerosis 1990; 10: 1067-1073
    CrossrefPubMedGoogle Scholar
  • 35 Mussoni L, Madema F, Camera M, Bernini F, Sironi L, Sirtori M, Tremoli E. Atherogenic lipoproteins and release of plasminogen activator inhibitor 1 (PAI-1) by endothelial cells. Fibrinolysis 1990; (Suppl. 02) 79-81
    PubMedGoogle Scholar
  • 36 Latron Y, Chautan M, Anfosso F, Alessi MC, Nalbone G, Lafont H, Juhan-Vague I. Stimulating effect of oxidized low density lipoprotein on plasminogen activator inhibitor 1 synthesis by endothelial cells. Arterioscler Thromb 1991; 11: 1821-1829
    CrossrefPubMedGoogle Scholar
  • 37 Etingin O, Hajjar D, Hajjar K, Harpel P, Nachman R. Lipoprotein(a) regulates plasminogen activator inhibitor-1 expression in endothelial cells: A potential mechanism in thrombogenesis. J Biol Chem 1991; 266: 2459-2465
    PubMedGoogle Scholar
  • 38 Juhan-Vague I, Alessi MC. Plasminogen activator inhibitor 1 and athero-thrombosis. Thromb Haemost 1993; 70: 138-143
    Article in Thieme ConnectPubMedGoogle Scholar
  • 39 Francis RB, Kawanishi D, Baruch T, Mahrer P, Rahimtoola S, Feinstein DI. Impaired fibrinolysis in coronary artery disease. Am Heart J 1988; 115: 776-780
    CrossrefPubMedGoogle Scholar
  • 40 Sanchez-Bayle M, Cocho P, Baeza J, Vila S. Fibrinogen as a cardiovascular risk factor in Spanish children and adolescents. Am Heart J 1993; 126: 322-326
    CrossrefPubMedGoogle Scholar
  • 41 Rallidis L, Papageorgakis N, Megalou A, Anagnostou E, Chatzidimitriou G, Tsitouris G. Fibrinogen in the offspring of men with premature coronary artery disease. Eur Heart J 1995; 16: 1814-1818
    CrossrefPubMedGoogle Scholar
  • 42 Thompson WD, Smith EB. Atherosclerosis and the coagulation system. J Pathol 1989; 159: 97-106
    CrossrefPubMedGoogle Scholar
  • 43 Bini A, Fenoglio JJ, Mesa-Tejada R, Kudryk B, Kaplan KL. Identification and distribution of fibrinogen, fibrin and fibrin(ogen) degradation products in atherosclerosis: Use of monoclonal antibodies. Arteriosclerosis 1989; 9: 109-121
    CrossrefPubMedGoogle Scholar