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Age and aerobic training status effects on plasma and skeletal muscle tPA and PAI-1

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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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Authors and Affiliations

  1. Human Energy Research Laboratory, Department of Kinesiology, Michigan State University, East Lansing, MI, 48824, USA

    Ryan M. Francis, Christine L. Romeyn, Adam M. Coughlin, Paul R. Nagelkirk, Christopher J. Womack & Jeffrey T. Lemmer

  2. Department of Movement Science, Grand Valley State University, Allendale, MI, 49401, USA

    Jeffrey T. Lemmer

Authors
  1. Ryan M. Francis
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  2. Christine L. Romeyn
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  3. Adam M. Coughlin
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  4. Paul R. Nagelkirk
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  5. Christopher J. Womack
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  6. Jeffrey T. Lemmer
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Corresponding author

Correspondence to Jeffrey T. Lemmer.

Additional information

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

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