RSS-Feed abonnieren
DOI: 10.1055/s-2005-865813
© Georg Thieme Verlag KG Stuttgart · New York
Genetic Markers of Fibrinolytic Responses of Older Persons to Exercise Training
Publikationsverlauf
Accepted after revision: June 15, 2005
Publikationsdatum:
30. August 2005 (online)
![](https://www.thieme-connect.de/media/sportsmed/200608/lookinside/thumbnails/10.1055-s-2005-865813-1.jpg)
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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
PhD James Hagberg
Department of Kinesiology
University of Maryland
College Park, MD 20742-2611
USA
Telefon: + 3014052487
Fax: + 30 14 05 55 78
eMail: hagberg@umd.edu