Abstract
The plasminogen system, which includes tissue type plasminogen activator (tPA), urokinase type plasminogen activator (uPA), and their main inhibitor, plasminogen activator inhibitor type 1 (PAI-1), plays a major role in both fibrinolysis and tissue remodeling. This study compares the levels of tPA, uPA, and PAI-1 at the groin and ankle in normal and varicose greater saphenous vein (GSV). GSV was collected from patients undergoing varicose vein (VV) removal and from normal vein (NV) from arterial bypass procedures. Portions of the GSV at the groin and the ankle were minced and placed in serum-free media for 48 hours. Assays of the supernatants were obtained for tPA, uPA, and PAI-1 protein by enzyme-linked immunosorbent assay. Cyclohexamide and actinomycin D were also added to the media of the VV tissue explant supernatants to inhibit protein and RNA synthesis, respectively. Levels of tPA were significantly higher at the groin (11 +/- 2) than the ankle (5 +/- 1) in the VV (p < 0.005), and this trend was also seen in the NV (groin 10 +/- 2 and ankle 7 +/- 3). Levels of uPA were significantly higher in the groin VV (14 +/- 4.3) than in NV (3.0 +/- 0.8, p < 0.05). This difference, although not statistically significant, applied to the ankle as well (VV 14.5 +/- 6.3 and NV 5.3 +/- 2.7). No significant difference was seen between NV and VV for PAI-1 (NV, groin 155 +/- 73 and ankle 113 +/- 53, VV, groin 161 +/- 20 and ankle 142 +/- 38) or tPA. Inhibitor studies revealed no significant difference among control, cyclohexamide, and actinomycin D supernatants for tPA, suggesting release of protein rather than active synthesis. In contrast, inhibitor supernatants were significantly lower for uPA and PAI-1 than control supernatants (p < 0.05), suggesting that uPA and PAI-1 were actively synthesized. In the tissue explant supernatant model uPA and PAI-1 are actively synthesized, but tPA is not. Levels of PAI-1 were comparable in all four groups. Levels of uPA in the varicose GSV were higher than in NV, suggesting a role for uPA in the pathologic makeup of VV. Levels of tPA were higher at the groin versus the ankle position, potentially explaining the previously described increased fibrinolytic activity seen at the groin.
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