Shireman P K, McCarthy W J, Pearce W H, Shively V P, Cipollone M, Kwaan H C, Yao J S
Department of Surgery, Northwestern University School of Medicine, Chicago, IL 60611, USA.
J Vasc Surg. 1996 Nov;24(5):719-24. doi: 10.1016/s0741-5214(96)70003-4.
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.
纤溶酶原系统包括组织型纤溶酶原激活剂（tPA）、尿激酶型纤溶酶原激活剂（uPA）及其主要抑制剂1型纤溶酶原激活剂抑制剂（PAI-1），在纤维蛋白溶解和组织重塑中均起主要作用。本研究比较正常和曲张大隐静脉（GSV）腹股沟和踝关节处tPA、uPA和PAI-1的水平。
从接受静脉曲张（VV）切除术的患者以及动脉搭桥手术中的正常静脉（NV）中采集GSV。将腹股沟和踝关节处的部分GSV切碎，置于无血清培养基中48小时。通过酶联免疫吸附测定法检测上清液中tPA、uPA和PAI-1蛋白。还向VV组织外植体上清液的培养基中添加环己酰胺和放线菌素D，分别抑制蛋白质和RNA合成。
VV组中腹股沟处tPA水平（11±2）显著高于踝关节处（5±1）（p<0.005），NV组也有此趋势（腹股沟10±2，踝关节7±3）。腹股沟处VV组uPA水平（14±4.3）显著高于NV组（3.0±0.8，p<0.05）。这种差异在踝关节处也存在，尽管无统计学意义（VV 14.5±6.3，NV 5.3±2.7）。PAI-1或tPA在NV组和VV组之间无显著差异（NV组，腹股沟155±73，踝关节113±53；VV组，腹股沟161±20，踝关节142±38）。抑制剂研究显示，tPA在对照、环己酰胺和放线菌素D上清液之间无显著差异，提示为蛋白质释放而非活性合成。相反，uPA和PAI-1的抑制剂上清液显著低于对照上清液（p<0.05），提示uPA和PAI-1是活性合成的。
在组织外植体上清液模型中，uPA和PAI-1是活性合成的，但tPA不是。所有四组中PAI-1水平相当。曲张GSV中uPA水平高于NV，提示uPA在VV病理构成中起作用。腹股沟处tPA水平高于踝关节处，这可能解释了先前所述腹股沟处纤维蛋白溶解活性增加的现象。
