LeBoeuf R D, Gregg R R, Weigel P H, Fuller G M
Department of Human Biological Chemistry and Genetics, University of Texas Medical Branch, Galveston 77550.
Biochemistry. 1987 Sep 22;26(19):6052-7. doi: 10.1021/bi00393a016.
Previously, we reported that the glycosaminoglycan (GAG) hyaluronic acid (HA) specifically bound to the plasma protein fibrinogen [LeBoeuf, R. D., Raja, R. R., Fuller, G. M., & Weigel, P. H. (1986) J. Biol. Chem. 261, 12586]. The binding of other macromolecules to fibrinogen could influence the conversion of fibrinogen to fibrin. Therefore, we tested whether HA and other GAGs could alter the kinetics of fibrin polymer formation and the physical structure of the resulting gel. In this study, we present data showing that the GAGs HA and chondroitin sulfate (CS) affect fibrin formation in three specific ways: (i) they decreased the clotting time of fibrinogen 3-10-fold; (ii) both GAGs increase significantly the rate of fibrin polymer formation; and (iii) fibrin gels containing HA or CS had a final A450 that was greater than controls, indicating that these two glycosaminoglycans influence either the final size of fibrin fibrils or the extent of the lateral association between fibrils. These results demonstrate that the interactions of HA and CS with forming fibrin polymers can alter both the kinetics of formation and may produce structural changes in fibrin gels.
此前，我们报道过糖胺聚糖（GAG）透明质酸（HA）能特异性结合血浆蛋白纤维蛋白原[勒伯夫，R.D.，拉贾，R.R.，富勒，G.M.，& 韦格尔，P.H.（1986年）《生物化学杂志》261卷，12586页]。其他大分子与纤维蛋白原的结合可能会影响纤维蛋白原向纤维蛋白的转化。因此，我们测试了HA和其他GAG是否会改变纤维蛋白聚合物形成的动力学以及所形成凝胶的物理结构。在本研究中，我们展示的数据表明，GAG中的HA和硫酸软骨素（CS）以三种特定方式影响纤维蛋白的形成：（i）它们将纤维蛋白原的凝血时间缩短了3至10倍；（ii）这两种GAG均显著提高了纤维蛋白聚合物的形成速率；（iii）含有HA或CS的纤维蛋白凝胶的最终A450大于对照组，这表明这两种糖胺聚糖会影响纤维蛋白原纤维的最终大小或纤维之间横向缔合的程度。这些结果表明，HA和CS与正在形成的纤维蛋白聚合物之间的相互作用既能改变形成动力学，也可能使纤维蛋白凝胶产生结构变化。
