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
Phone: + 3014052487
Fax: + 30 14 05 55 78
Email: hagberg@umd.edu