Effect of Gender and Aerobic Training Status on Plasma and Skeletal Muscle Fibrinolytic Potential

Abstract

Fibrinolysis is the capacity to lyse fibrin clots through the activity of the plasminogen system. Plasminogen is primarily activated into active plasmin by the enzyme tissue plasminogen activator (tPA), while this process is primarily inhibited by plasminogen activator inhibitor-1 (PAI-1). Endothelial cells are the primary site of tPA and PAI-1 synthesis and release. However, tPA and PAI-1 are expressed in skeletal muscle tissue, and PAI-1 is also expressed in adipose tissue. Both of these tissues are influenced by gender and aerobic exercise training. PURPOSE: To cross-sectionally investigate the effect of gender and aerobic exercise status on plasma and skeletal muscle expression of tPA and PAI-1. METHODS: Skeletal muscle and plasma tPA and PAI-1 gene expression were measured in four groups of young subjects; trained males (TM, n = 7, mean age 21.6 ± 0.4 y), untrained males (UM, n = 6, mean age 21.5 ± 0.4 y), trained females (TF, n = 8, mean age 24.4 ± 2.1 y), and untrained females (UF, n = 6, mean age 22.8 ± 1.2 y). To measure tPA and PAI-1 activity and antigen, 5 ml of venous blood were collected into an acidified citrate solution after a 12h fast. Women were tested 4 d post-menses. Samples were spun to obtain platelet-poor plasma and stored at −80C until assayed. All blood samples were obtained prior to the muscle biopsy procedure. Muscle samples were obtained from the vastus lateralis muscle via a percutaneous muscle biopsy following a 12-hour fast. Total RNA was extracted from the muscle samples, and subjected to reverse transcription. Skeletal muscle tPA and PAI-1 gene expression was then assessed by the polymerase chain reaction using gene specific primers. RESULTS: There was no affect of gender or aerobic training status on plasma tPA activity or antigen, muscle tPA RNA expression, or muscle PAI-1 RNA expression. There was a significant effect of training status on plasma PAI-1 activity, such that the trained groups had significantly lower PAI-1 activity compared to the untrained groups (6.0 ± 1.5 vs. 13.0 ± 2.1 IU/ml, p<0.05). Additionally, there was a significant inverse relationship between plasma PAI-1 activity and VO2max (r = −0.386, p < 0.05). CONCLUSIONS: Gender does not have an influence on plasma tPA activity or antigen, muscle RNA expression of tPA or PAI-1. Aerobic exercise does have a positive affect on fibrinolytic capacity, as evidenced by the lower PAI-1 activity in the trained subjects. This effect appears to be mediated through increased fitness level, as indicated by the negative correlation between VO2max and PAI-1 activity.