Baruch D, Ajzenberg N, Denis C, Legendre P, Lormeau J C, Meyer D
INSERM Unité 143, Hôpital de Bicêtre, Paris, France.
Thromb Haemost. 1994 Jan;71(1):141-6.
To investigate the influence of the structure of heparin on its binding to vWF, we compared heparin fractions of different molecular weight (MW) or affinity for antithrombin III (ATIII). We studied the interaction of purified 125I-vWF or plasma vWF, labeled with a pool of 125I-monoclonal antibodies to vWF, with unfractionated heparin immobilized on agarose beads. Fractions were compared as competitors of these interactions and their effect was quantitated by their half-maximal inhibition (IC50). When the MW of the fractions decreased, especially below 7500, their IC50 increased, indicating that the affinity of the fractions for vWF decreased with their MW. Using heparin-derived oligosaccharides, we also demonstrated that a minimal chain length of 18 monosaccharides was required for heparin binding to vWF. In addition, different fractions with low affinity for ATIII were compared as competitors of 125I-vWF binding to heparin-agarose. Despite a very low content of ATIII binding sites, some fractions retained a low IC50. Thus, heparin interaction with vWF is independent of the presence of the ATIII binding site and is mostly dependent on the length of the heparin chain. These data suggest that unfractionated heparin is a more potent inhibitor of vWF-dependent functions than low MW heparin fractions.
为了研究肝素结构对其与血管性血友病因子（vWF）结合的影响，我们比较了不同分子量（MW）或对抗凝血酶III（ATIII）亲和力的肝素组分。我们研究了纯化的125I-vWF或用一组针对vWF的125I单克隆抗体标记的血浆vWF与固定在琼脂糖珠上的未分级肝素之间的相互作用。将各组分作为这些相互作用的竞争者进行比较，并通过其半数最大抑制浓度（IC50）对其作用进行定量。当组分的分子量降低时，尤其是低于7500时，其IC50增加，这表明组分对vWF的亲和力随分子量降低而降低。使用。使用肝素衍生的寡糖，我们还证明肝素与vWF结合需要至少18个单糖的链长。此外，将对ATIII亲和力低的不同组分作为125I-vWF与肝素-琼脂糖结合的竞争者进行比较。尽管ATIII结合位点的含量非常低，但一些组分仍保持较低的IC50。因此，肝素与vWF的相互作用与ATIII结合位点的存在无关，主要取决于肝素链的长度。这些数据表明，未分级肝素比低分子量肝素组分更有效地抑制vWF依赖的功能。
