Download PDF
Int J Sports Med 2006; 27(8): 617-622
DOI: 10.1055/s-2005-865813
Training & Testing

© Georg Thieme Verlag KG Stuttgart · New York

Genetic Markers of Fibrinolytic Responses of Older Persons to Exercise Training

O. Kulaputana1 , I. Ghiu1 , D. A. Phares1 , R. E. Ferrell2 , R. F. Macko3 , A. P. Goldberg3 , J. M. Hagberg1
  • 1Department of Kinesiology, University of Maryland, College Park, MD, USA
  • 2Department of Human Genetics, University of Pittsburgh Graduate School of Public Health, Pittsburgh, PA, USA
  • 3Geriatric Research, Education, and Clinical Center, Baltimore VA Medical Center, Baltimore, MD, USA
Further Information

Publication History

Accepted after revision: June 15, 2005

Publication Date:
30 August 2005 (online)

Also available at
    Permissions and Reprints

Abstract

We assessed the interactive effect of genetic polymorphisms and exercise training on fibrinolysis in 50 - 75 yr old men (n = 17) and women (n = 28). Subjects had tissue plasminogen activator (t-PA) antigen levels and activity and plasminogen activator inhibitor-1 (PAI-1) activity measured before and after 6 mo of endurance-exercise training. Subject's DNA was typed for the PAI-1 4 G/5 G and t-PA I/D variants. Baseline PAI-1 activity, t-PA activity, and t-PA antigen levels were not different among PAI-1 or t-PA genotype groups. Overall, exercise training did not change PAI-1 activity (- 0.43 ± 0.81 IU/mL, p = NS), increased t-PA activity (0.37 ± 0.16 IU/mL, p = 0.02), and decreased t-PA antigen levels (- 0.88 ± 0.20 ng/mL, p < 0.001). Although the differences in changes with training were not significant among genotype groups, significant t-PA antigen level improvements were evident only in PAI-1 4 G allele carriers and significant t-PA activity increases only in PAI-1 4 G homozygotes. t-PA genotype affected the training-induced t-PA antigen level improvements (p = 0.033) after covarying for gender and baseline t-PA antigen levels, with the smallest and largest reductions in the D homozygotes and I/D heterozygotes, respectively. These findings could have important treatment implications for the use of exercise training to reduce CV disease and thrombotic risk in older men and women.

Key words

PAI-1 activity - t-PA antigen - PAI-1 genotype - t-PA genotype

References

  • 1 American College of Sports Medicine .Guidelines for Exercise Testing and Prescription. Indianapolis, IN; American College of Sports Medicine 1991: 35-45
    Google Scholar
  • 2 Blair S N, Kohl III H W, Paffenbarger Jr R S, Clark D G, Cooper K H, Gibbons L W. Physical fitness and all-cause mortality: a prospective study of healthy men and women.  J Am Med Assoc. 1989;  262 2395-2401
    CrossrefPubMedGoogle Scholar
  • 3 Chandler W L, Schwartz R S, Stratton J R, Vitiello M V. Effects of endurance training on the circadian rhythm of fibrinolysis in men and women.  Med Sci Sports Exerc. 1996;  28 647-655
    PubMedGoogle Scholar
  • 4 Cortellaro M, Cofrancesco E, Boschetti C, Mussoni L, Donati M B, Cardillo M, Catalano M, Gabrielli L, Lombardi B, Specchia G. Increased fibrin turnover and high PAI-1 activity as predictors of ischemic events in atherosclerotic patients A case-control study. The PLAT Group.  Arterioscler Thromb. 1993;  13 1412-1417
    PubMedGoogle Scholar
  • 5 Dawson S J, Wiman B, Hamsten A, Green F, Humphries S, Henney A M. 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 10739-10745
    PubMedGoogle Scholar
  • 6 DeGeus E, Kluft C, DeBa V DL. Effects of exercise training on plasminogen activator inhibitor activity.  Med Sci Sports Exerc. 1992;  24 1210-1219
    PubMedGoogle Scholar
  • 7 Doggen C, Bertina R, Cats V, Reitsma P, Rosendaal F. The 4 G/5 G polymorphism in the plasminogen activator inhibitor-1 gene is not associated with myocardial infarction.  Thrombosis Haemost. 1999;  82 115-120
    PubMedGoogle Scholar
  • 8 El-Sayed M, Lin X, Rattu A. Blood coagulation and fibrinolysis at rest and in response to maximal exercise before and after a physical conditioning programme.  Blood Coagul Fibrinolysis. 1995;  6 747-752
    CrossrefPubMedGoogle Scholar
  • 9 Eriksson P, Kallin B, van't Hooft F M, 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 USA. 1995;  92 1851-1855
    CrossrefPubMedGoogle Scholar
  • 10 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 Thrombrosis Vasc Biol. 1998;  18 20-26
    PubMedGoogle Scholar
  • 11 Estelles A, Aznar J, Tormo G, Sapena P, Tormo V, Espana F. Influence of a rehabilitation sports programme on the fibrinolytic activity of patients after myocardial infarction.  Thrombosis Research. 1989;  55 203-212
    CrossrefPubMedGoogle Scholar
  • 12 Hamsten A, DeFaire U, Walldius G, Dahlen G, Szamosi A, Landou C, Blomback M, Wiman B. Plasminogen activator inhibitor in plasma: risk factor for recurrent myocardial infarction.  Lancet. 1987;  2 3-9
    PubMedGoogle Scholar
  • 13 Henry M, Chomiki N, Scarabin P Y, Alessi M C, Peiretti F, Arveiler D, Ferrieres J, Evans A, Amouyel P, Poirier O, Cambien F, Juhan-Vague I. Five frequent polymorphisms of the PAI-1 gene: lack of association between genotypes, PAI activity, and triglyceride levels in a healthy population.  Arterioscler Thrombrosis Vasc Biol. 1997;  17 851-858
    PubMedGoogle Scholar
  • 14 Henry M, Tregouet D A, Alessi M C, Aillaud M F, Visvikis S, Siest G, Tiret L, Juhan-Vague I. Metabolic determinants are much more important than genetic polymorphisms in determining the PAI-1 activity and antigen plasma concentrations: a family study with part of the Stanislas Cohort.  Thrombrosis Vasc Biol. 1998;  18 84-91
    PubMedGoogle Scholar
  • 15 Hooper W C, Lally C, Austin H, Renshaw M, Dilley A, Wenger N, Phillips D, Whitsett C, Rawlins P, Evatt B. The role of the t-PA I/D and PAI-1 4 G/5 G polymorphisms in African-American adults with a diagnosis of myocardial infarction or venous thromboembolism.  Thromb Res. 2000;  99 223-230
    CrossrefPubMedGoogle Scholar
  • 16 Iacoviello L, Di Castelnuovo A, de Knijff P. Alu-repeat polymorphism in the t-PA gene, t-PA levels and the risk of familial AMI.  Fibrinolysis. 1996;  10 13-18
    PubMedGoogle Scholar
  • 17 Jern C, Ladenvall P, Wall U, Jern S. Gene polymorphism of t-PA is associated with forearm vascular t-PA release rate.  Arterioscler Thrombrosis Vasc Biol. 1999;  19 454-459
    PubMedGoogle Scholar
  • 18 Juhan-Vague I, Pyke S D, Alessi M C, Jespersen J, Haverkate F, Thompson S G. Fibrinolytic factors and the risk of myocardial infarction or sudden death in patients with angina pectoris. ECAT study group.  Circulation. 1996;  94 2057-2063
    CrossrefPubMedGoogle Scholar
  • 19 Krauss R M, Deckelbaum R J, Ernst N. Dietary guidelines for healthy American adults. A statement for health professionals from the Nutrition Committee, American Heart Association.  Circulation. 1996;  94 1795-1800
    CrossrefPubMedGoogle Scholar
  • 20 Margaglione M, Grandone E, Cappucci G, Colaizzo D, Giuliani N, Vecchione G, d'Addedda M, Di M. An alternative method for PAI-1 promoter polymorphism (4 G/5 G) typing.  Thrombosis Haemost. 1997;  77 605-606
    PubMedGoogle Scholar
  • 21 Rankinen T, Rauramaa R, Vaisanen S, Halonen P, Penttila I. Blood coagulation and fibrinolytic factors are unchanged by aerobic exercise or fat modified diet.  Fibrinolysis. 1994;  8 48-53
    PubMedGoogle Scholar
  • 22 Ridker P M, Hennekens C H, Stampfer M J, Manson J E, Vaughan D E. Prospective study of endogenous tissue plasminogen activator and risk of stroke.  Lancet. 1994;  343 940-943
    CrossrefPubMedGoogle Scholar
  • 23 Ridker P M, Vaughan D E, Stampfer M J, Manson J E, Hennekens C H. Endogenous tissue-type plasminogen activator and risk of myocardial infarction.  Lancet. 1993;  341 1165-1168
    CrossrefPubMedGoogle Scholar
  • 24 Speiser W, Langer W, Pschaick A. Increased blood fibrinolytic activity after physical exercise: comparative study in individuals with different sporting activities and in patients after myocardial infarction taking part in a rehabilitation sports program.  Thrombosis Research. 1988;  55 203-212
    PubMedGoogle Scholar
  • 25 Stratton J R, Chandler W L, Schwartz R S. Effects of physical conditioning on fibrinolytic variables and fibrinogen in young and old healthy adults.  Circulation. 1991;  83 1692-1697
    CrossrefPubMedGoogle Scholar
  • 26 Vaisanen S B, Humphries S E, Luong L A, Penttila I, Bouchard C, Rauramaa R. Regular exercise, plasminogen activator inhibitor-1 activity and the 4 G/5 G promoter polymorphism in the PAI-1 gene.  Thrombosis Haemost. 1999;  82 1117-1120
    PubMedGoogle Scholar
  • 27 van den Eijnden-Schrauwen Y, Lakenberg N, Emeis J J, de Knijff P. Alu-repeat polymorphism in the tissue-type plasminogen activator (t-PA) gene does not affect basal endothelial t-PA synthesis.  Thrombosis Haemost. 1995;  74 1202-1208
    PubMedGoogle Scholar
  • 28 van der Bom J G, de Knijff P, Haverkate F, Bots M, Meijer P, de Jong P T, Hofman A, Kluft C, Grobbee D E. Tissue plasminogen activator and risk of myocardial infarction. The Rotterdam Study.  Circulation. 1997;  95 2623-2627
    PubMedGoogle Scholar
  • 29 Wilund K R, Colvin P L, Phares D, Goldberg A P, Hagberg J M. The effect of endurance exercise training on plasma lipoprotein AI and lipoprotein AI:AII concentrations in sedentary adults.  Metabolism. 2002;  51 1053-1060
    CrossrefPubMedGoogle Scholar
  • 30 Ye S, Green F R, Scarabin P Y, Nicaud V, Bara L, Dawson S J, Humphries S E, Evans A, Luc G, Cambou J P. The 4 G/5 G genetic polymorphism in the promoter of the plasminogen activator inhibitor-1 (PAI-1) gene is associated with differences in plasma PAI-1 activity but not with risk of myocardial infarction in the ECTIM study.  Thrombosis Haemost. 1995;  74 837-841
    PubMedGoogle Scholar

PhD James Hagberg

Department of Kinesiology
University of Maryland

College Park, MD 20742-2611

USA

Phone: + 3014052487

Fax: + 30 14 05 55 78

Email: hagberg@umd.edu

      >