Abstract
Introduction
Reductions in fibrinolytic potential occur with both aging and physical inactivity and are associated with an increased cardiovascular disease risk. Plasmin, the enzyme responsible for the enzymatic degradation of fibrin clots, is activated by tissue plasminogen activator (tPA), while plasminogen activator inhibitor-1 (PAI-1) inhibits its activation. Currently, fibrinolysis research focuses almost exclusively on changes within the plasma. However, tPA and PAI-1 are expressed by human skeletal muscle (SM). Currently, no studies have focused on changes in SM fibrinolytic activity with regard to aging and aerobic fitness.
Purpose
The purpose of this study was to cross-sectionally evaluate effects of age and aerobic fitness on tPA and PAI-1 expressions and activity in SM.
Methods
Twenty-six male subjects were categorized into the following groups: (1) young aerobically trained (n = 8); (2) older aerobically trained (n = 6); (3) young aerobically untrained (n = 7); and (4) older aerobically untrained (n = 5). Muscle biopsies were obtained from each subject. SM tPA activity was assessed using gel zymography and SM tPA and PAI-1 expressions were assessed using RT-PCR.
Results
Trained subjects had higher SM tPA activity compared to untrained (25.3 ± 2.4 × 103 vs. 21.5 ± 5.6 × 103 pixels, respectively; p = 0.03) with no effect observed for age. VO2 max and SM tPA activity were also significantly correlated (r = 0.42; p < 0.04). SM tPA expression was higher in older participants, but no effect of fitness level was observed. No differences were observed for PAI-1 expression in SM.
Conclusions
Higher levels of aerobic fitness are associated with increased fibrinolytic activity in SM.
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Abbreviations
- CVD:
-
Cardiovascular disease
- OT:
-
Older trained
- OU:
-
Older untrained
- PAI-1:
-
Plasminogen activator inhibitor-1
- PCR:
-
Polymerase chain reaction
- RCF:
-
Relative centrifugal force
- RNA:
-
Ribonucleic acid
- RT:
-
Reverse transcription
- SM:
-
Skeletal muscle
- tPA:
-
Tissue plasminogen activator
- uPA:
-
Urokinase plasminogen activator
- VO2 max :
-
Maximal oxygen consumption
- wt:
-
Weight
- YT:
-
Young trained
- YU:
-
Young untrained
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Acknowledgments
This study was supported by a research grant from the Michigan State University Intramural Research Grant Program and the College of Education. We would like to thank Dr. Mukta Webber and Erik Tokar for their helping with teaching us gel zymography. We would like to thank the Research Technology Support Facility at Michigan State University for their consultation and expertise on the microarray analyses.
Conflict of interest
There are no companies, manufacturers or outside organizations that will benefit from the results of the present study.
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Communicated by Fabio Fischetti.
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Francis, R.M., Romeyn, C.L., Coughlin, A.M. et al. Age and aerobic training status effects on plasma and skeletal muscle tPA and PAI-1. Eur J Appl Physiol 114, 1229–1238 (2014). https://doi.org/10.1007/s00421-014-2857-2
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DOI: https://doi.org/10.1007/s00421-014-2857-2