Saelman E U, Hese K M, Nieuwenhuis H K, Uzan A, Cavero I, Marguerie G, Sixma J J, de Groot P G
Department of Hematology, University Hospital Utrecht, The Netherlands.
Arterioscler Thromb. 1993 Aug;13(8):1164-70. doi: 10.1161/01.atv.13.8.1164.
The effect of D-Arg-Gly-Asp-Trp (dRGDW), a synthetic RGD-containing peptide, on platelet adhesion and aggregate formation on various purified adhesive proteins and the extracellular matrix of endothelial cells was investigated with anticoagulated blood recirculating through a parallel-plate perfusion chamber. Aggregate formation on the extracellular matrix of phorbol myristate acetate (PMA)-stimulated endothelial cells and on collagen type I was more strongly inhibited by dRGDW at higher shear rates than at a low shear rate. Platelet adhesion to the extracellular matrix of nonactivated and PMA-stimulated endothelial cells was inhibited by dRGDW, especially at high shear rates, probably as a consequence of the inhibition of platelet spreading. Inhibition by dRGDW of platelet adhesion to von Willebrand factor, fibronectin, and fibrinogen was almost complete, indicating that platelet adhesion to these substrates is mediated through RGD-directed receptors. Platelet adhesion to laminin was not inhibited by the peptide, whereas platelet adhesion to collagen was increased as a consequence of the inhibition of aggregate formation. Our results show that dRGDW is a strong inhibitor of platelet adhesion and aggregate formation, especially at high shear rates.
通过抗凝血液在平行板灌注室中循环，研究了合成的含RGD肽D-Arg-Gly-Asp-Trp（dRGDW）对血小板在各种纯化的黏附蛋白和内皮细胞细胞外基质上的黏附及聚集体形成的影响。在较高剪切速率下，dRGDW对佛波酯（PMA）刺激的内皮细胞细胞外基质和I型胶原上的聚集体形成的抑制作用比低剪切速率时更强。dRGDW抑制血小板对未活化和PMA刺激的内皮细胞细胞外基质的黏附，尤其是在高剪切速率下，这可能是血小板铺展受到抑制的结果。dRGDW对血小板与血管性血友病因子、纤连蛋白和纤维蛋白原的黏附抑制作用几乎是完全的，表明血小板对这些底物的黏附是通过RGD导向的受体介导的。该肽不抑制血小板对层粘连蛋白的黏附，而由于聚集体形成受到抑制，血小板对胶原的黏附增加。我们的结果表明，dRGDW是血小板黏附和聚集体形成的强抑制剂，尤其是在高剪切速率下。
