Royal College of Surgeons in Ireland, Dublin, Ireland.
Arterioscler Thromb Vasc Biol. 2012 Jul;32(7):1724-31. doi: 10.1161/ATVBAHA.112.250464. Epub 2012 Apr 26.
Thrombosis occurs at sites of vascular injury when platelets adhere to subendothelial matrix proteins and to each other. Platelets express many surface receptor proteins, the function of several of these remains poorly characterized. Cadherin 6 is expressed on the platelet surface and contains an arginine-glycine-aspartic acid motif, suggesting that it might have a supportive role in thrombus formation. The aim of this study was to characterize the role of cadherin 6 in platelet function.
Platelet aggregation was inhibited by both antibodies and exogenous soluble cadherin 6. Platelet adhesion to immobilized cadherin 6 was inhibited by arginine-glycine-aspartic acid-serine tetrapeptides. Antibodies to α(IIb)β(3) inhibited platelet adhesion to cadherin 6. Because platelet aggregation occurs in fibrinogen and von Willebrand factor double-deficient mice, we investigated whether cadherin 6 is an alternative ligand for the integrin α(IIb)β(3). Platelet aggregation in fibrinogen and von Willebrand factor double-deficient mice was significantly inhibited by an antibody to cadherin 6. In flow-based assays, inhibition of cadherin 6 caused a marked reduction in thrombus formation in both human and mouse blood.
This study demonstrates the role of cadherin 6 as a novel ligand for α(IIb)β(3) and highlights its function in thrombus formation.
当血小板黏附于血管内皮细胞下基质蛋白和彼此之间时，血栓会在血管损伤部位形成。血小板表达许多表面受体蛋白，其中一些的功能仍未得到很好的描述。钙黏蛋白 6 表达于血小板表面，且含有精氨酸-甘氨酸-天冬氨酸基序，这表明它可能在血栓形成中具有支持作用。本研究旨在探讨钙黏蛋白 6 在血小板功能中的作用。
抗体和外源性可溶性钙黏蛋白 6 均可抑制血小板聚集。精氨酸-甘氨酸-天冬氨酸-丝氨酸四肽可抑制血小板黏附于固定化钙黏蛋白 6。抗 α(IIb)β(3)抗体抑制血小板黏附于钙黏蛋白 6。由于血小板聚集发生在纤维蛋白原和血管性血友病因子双重缺陷小鼠中，我们研究了钙黏蛋白 6 是否是整合素 α(IIb)β(3)的替代配体。在纤维蛋白原和血管性血友病因子双重缺陷小鼠中，抗钙黏蛋白 6 抗体显著抑制了血小板聚集。在基于流动的测定中，钙黏蛋白 6 的抑制导致人血和鼠血中血栓形成明显减少。
本研究证明了钙黏蛋白 6 作为整合素 α(IIb)β(3)的新型配体的作用，并强调了其在血栓形成中的功能。
