Galewska Zofia, Bańkowski Edward, Romanowicz Lech, Jaworski Stefan
Department of Medical Biochemistry, Medical Academy of Białystok, ul. Mickiewicza 2, 15-089 Białystok, Poland.
Clin Chim Acta. 2003 Sep;335(1-2):109-15. doi: 10.1016/s0009-8981(03)00296-1.
It was found in our previous paper that pre-eclampsia-associated accumulation of collagen in the umbilical cord artery (UCA) is a result of increased biosynthesis and decreased degradation of this protein. It is known that the activity of collagenolytic enzymes is a main factor regulating collagen degradation rate in various tissues.
For this reason it was decided to evaluate the effect of pre-eclampsia on the content and activity of metalloproteinases by immunoenzymatic method (ELISA), zymographic technique and with the use of specific substrates.
A low amount of MMP-1 (collagenase 1), MMP-9 (gelatinase B) and MMP-3 (stromelysin 1) was detected in the extracts from the wall of the umbilical cord artery. MMP-2 (gelatinase A) is the main collagenolytic enzyme in UCA wall (both latent and active form). Pre-eclampsia is associated with a distinct reduction in those metalloproteinases content in comparison to control UCAs. It can be concluded from zymography that MMP-2 (gelatinase A) of the umbilical cord artery forms an inactive complex with a tissue inhibitor of metalloproteinases (TIMP). Such a complex dissociates under the action of p-aminophenylmercuric acetate (APMA) or sodium dodecyl sulphate.
The decrease of metalloproteinases content and activity in the umbilical cord artery may be a factor that reduces the breakdown of collagen in the arterial wall and promotes the accumulation of this protein. The accumulation of collagen with simultaneous reduction in elastin content in the UCA may be the factor that reduces the elasticity of arterial wall and decreases the blood flow in the fetus of women with pre-eclampsia.
我们之前的论文发现，子痫前期相关的脐动脉（UCA）中胶原蛋白积累是该蛋白生物合成增加和降解减少的结果。已知胶原酶的活性是调节各种组织中胶原蛋白降解速率的主要因素。
因此，决定通过免疫酶法（ELISA）、酶谱技术和使用特定底物来评估子痫前期对金属蛋白酶含量和活性的影响。
在脐动脉壁提取物中检测到少量基质金属蛋白酶-1（胶原酶1）、基质金属蛋白酶-9（明胶酶B）和基质金属蛋白酶-3（基质溶解素1）。基质金属蛋白酶-2（明胶酶A）是脐动脉壁中的主要胶原酶（包括潜伏形式和活性形式）。与对照脐动脉相比，子痫前期与这些金属蛋白酶含量的明显降低有关。从酶谱分析可以得出结论，脐动脉的基质金属蛋白酶-2（明胶酶A）与金属蛋白酶组织抑制剂（TIMP）形成无活性复合物。这种复合物在对氨基苯基汞乙酸盐（APMA）或十二烷基硫酸钠的作用下解离。
脐动脉中金属蛋白酶含量和活性的降低可能是减少动脉壁中胶原蛋白分解并促进该蛋白积累的一个因素。脐动脉中胶原蛋白积累同时弹性蛋白含量降低可能是降低子痫前期孕妇胎儿动脉壁弹性并减少血流的因素。
