Coppinger Judith A, Cagney Gerard, Toomey Sinead, Kislinger Thomas, Belton Orina, McRedmond James P, Cahill Dolores J, Emili Andrew, Fitzgerald Desmond J, Maguire Patricia B
Department of Clinical Pharmacology, Royal College of Surgeons in Ireland, 123 St Stephen's Green, Dublin 2, Ireland.
Blood. 2004 Mar 15;103(6):2096-104. doi: 10.1182/blood-2003-08-2804. Epub 2003 Nov 20.
Proteins secreted by activated platelets can adhere to the vessel wall and promote the development of atherosclerosis and thrombosis. Despite this biologic significance, however, the complement of proteins comprising the platelet releasate is largely unknown. Using a proteomics approach, we have identified more than 300 proteins released by human platelets following thrombin activation. Many of the proteins identified were not previously attributed to platelets, including secretogranin III, a potential monocyte chemoattractant precursor; cyclophilin A, a vascular smooth muscle cell growth factor; calumenin, an inhibitor of the vitamin K epoxide reductase-warfarin interaction, as well as proteins of unknown function that map to expressed sequence tags. Secretogranin III, cyclophilin A, and calumenin were confirmed to localize in platelets and to be released upon activation. Furthermore, while absent in normal vasculature, they were identified in human atherosclerotic lesions. Therefore, these and other proteins released from platelets may contribute to atherosclerosis and to the thrombosis that complicates the disease. Moreover, as soluble extracellular proteins, they may prove suitable as novel therapeutic targets.
活化血小板分泌的蛋白质可黏附于血管壁，促进动脉粥样硬化和血栓形成。然而，尽管具有这种生物学意义，但构成血小板释放物的蛋白质成分在很大程度上仍不清楚。我们采用蛋白质组学方法，鉴定出了凝血酶激活后人血小板释放的300多种蛋白质。许多鉴定出的蛋白质以前未被认为是血小板所具有的，包括分泌粒蛋白III（一种潜在的单核细胞趋化因子前体）、亲环素A（一种血管平滑肌细胞生长因子）、钙网蛋白（维生素K环氧化物还原酶与华法林相互作用的抑制剂），以及与表达序列标签对应的功能未知的蛋白质。分泌粒蛋白III、亲环素A和钙网蛋白被证实定位于血小板中，并在激活时释放。此外，它们在正常脉管系统中不存在，但在人类动脉粥样硬化病变中被鉴定出来。因此，血小板释放的这些及其他蛋白质可能促成动脉粥样硬化以及使该疾病复杂化的血栓形成。而且，作为可溶性细胞外蛋白质，它们可能被证明适合作为新型治疗靶点。
