Giordano Arturo, Musumeci Giuseppe, D'Angelillo Anna, Rossini Roberta, Zoccai Giuseppe Biondi, Messina Stefano, Coscioni Enrico, Romano Simona, Romano Maria Fiammetta
Department of Molecular Medicine and Medical Biotechnologies, Federico II University, Naples, Italy.
Curr Drug Metab. 2016;17(2):194-203. doi: 10.2174/1389200217666151211121112.
The use of inhibitors of glycoprotein IIb/IIIa (GPIIb/IIIa) has provided dramatic results in terms of the prevention of acute stent thrombosis and a reduction in major adverse coronary events in patients subjected to percutaneous coronary intervention. GPIIb/IIIa or αIIbβ3 is a member of the β3 subfamily of integrins, which also includes αVβ3. GPIIb/IIIa functions as a receptor for fibrinogen and several adhesion proteins sharing an arginine-glycine-aspartic acid (RGD) sequence. GPIIb/IIIa antagonists, through blockade of the receptor, prevent platelet aggregation. Among the three GPIIb/IIIa antagonists used in therapy, abciximab is an anti-β3 monoclonal antibody, while tirofiban and eptifibatide mimic the binding sequence of the fibrinogen ligand. Although antiplatelet aggregation represents the central function of GPIIb/IIIa inhibitors, further actions have been documented for these compounds.
The aim of the present article is to review the structures and functions of GPIIb/IIIa antagonists and to highlight the clinical outcomes and results of randomized trials with these compounds. Hypotheses on the unexplored potential of GPIIb/IIIa antagonists will be put forward.
GPIIb/IIIa inhibitors were developed to prevent platelet aggregation, however, these compounds can exert further biological functions, both platelet- and non-platelet-related. Large-scale studies comparing the efficacy and safety of GPIIb/IIIa antagonists are lacking. More insights into the functions of these compounds may lead to generation of novel small molecules able to antagonize platelet aggregation while promoting vascular repair.
糖蛋白IIb/IIIa(GPIIb/IIIa)抑制剂在预防急性支架血栓形成以及减少接受经皮冠状动脉介入治疗患者的主要不良冠状动脉事件方面取得了显著成效。GPIIb/IIIa或αIIbβ3是整合素β3亚家族的成员,该亚家族还包括αVβ3。GPIIb/IIIa作为纤维蛋白原和几种具有精氨酸-甘氨酸-天冬氨酸(RGD)序列的黏附蛋白的受体发挥作用。GPIIb/IIIa拮抗剂通过阻断该受体来预防血小板聚集。在用于治疗的三种GPIIb/IIIa拮抗剂中,阿昔单抗是一种抗β3单克隆抗体,而替罗非班和依替巴肽模拟纤维蛋白原配体的结合序列。尽管抗血小板聚集是GPIIb/IIIa抑制剂的核心功能,但已证明这些化合物还有其他作用。
本文旨在综述GPIIb/IIIa拮抗剂的结构与功能,并着重介绍使用这些化合物的随机试验的临床结果。将提出关于GPIIb/IIIa拮抗剂未被探索潜力的假设。
GPIIb/IIIa抑制剂的研发目的是预防血小板聚集,然而,这些化合物可发挥进一步的生物学功能,包括与血小板相关和与非血小板相关的功能。目前缺乏比较GPIIb/IIIa拮抗剂疗效和安全性的大规模研究。对这些化合物功能的更多深入了解可能会催生新型小分子,既能拮抗血小板聚集又能促进血管修复。