title: Age and aerobic training status effects on plasma and skeletal muscle tPA and PAI-1.
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  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 × 10(3) vs. 21.5 ± 5.6 × 10(3) 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.
authors.affiliation: Human Energy Research Laboratory, Department of Kinesiology, Michigan State University, East Lansing, MI, 48824, USA.
authors.forename: Ryan M
authors.initials: RM
authors.lastname: Francis
authors.forename: Christine L
authors.initials: CL
authors.lastname: Romeyn
authors.forename: Adam M
authors.initials: AM
authors.lastname: Coughlin
authors.forename: Paul R
authors.initials: PR
authors.lastname: Nagelkirk
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Womack
authors.forename: Jeffrey T
authors.initials: JT
authors.lastname: Lemmer
mesh_terms: D000367:Age Factors; D000368:Aged; D016022:Case-Control Studies; D015444:Exercise; D006801:Humans; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000378:metabolism / Q000502:physiology*; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D010959:Tissue Plasminogen Activator / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D055815:Young Adult
chemical_list: D017395:Plasminogen Activator Inhibitor 1; D012333:RNA, Messenger; C051321:SERPINE1 protein, human; D010959:Tissue Plasminogen Activator