Department of Chemistry, Faculty of Organic Chemistry & Biochemistry, University of Ioannina, Ioannina, Greece.
Protein Pept Lett. 2021;28(9):983-995. doi: 10.2174/0929866528666210505120659.
The main role of platelets is to contribute to hemostasis. However, under pathophysiological conditions, platelet activation may lead to thrombotic events of cardiovascular diseases. Thus, anti-thrombotic treatment is important in patients with cardiovascular disease. This review focuses on a platelet receptor, a transmembrane protein, the Multidrug Resistance Protein 4, MRP4, which contributes to platelet activation, by extruding endogenous molecules responsible for their activation and accumulation. The regulation of the intracellular concentration levels of these molecules by MRP4 turned to make the protein suspicious and at the same time an interesting regulatory factor of platelet normal function. Especially, the possible role of MRP4 in the excretion of xenobiotic and antiplatelet drugs such as aspirin is discussed, thus imparting platelet aspirin tolerance and correlating the protein with the ineffectiveness of aspirin antiplatelet therapy. Based on the above, this review finally underlines that the development of a highly selective and targeted strategy for platelet MRP4 inhibition will also lead to inhibition of platelet activation and accumulation.
血小板的主要作用是有助于止血。然而，在病理生理条件下，血小板的激活可能导致心血管疾病的血栓事件。因此，抗血栓治疗对心血管疾病患者很重要。这篇综述重点介绍了一种血小板受体，一种跨膜蛋白多药耐药蛋白 4（MRP4），它通过将负责其激活和积累的内源性分子排出细胞外，促进血小板的激活。MRP4 调节这些分子的细胞内浓度水平，这使得该蛋白成为一个可疑的靶点，同时也是血小板正常功能的一个有趣的调节因子。特别是，MRP4 在排泄阿司匹林等抗血小板药物和外来物方面的可能作用，从而赋予血小板对阿司匹林的耐受性，并将该蛋白与阿司匹林抗血小板治疗的无效性联系起来。基于上述内容，本文最后强调，开发针对血小板 MRP4 的高度选择性和靶向抑制策略也将抑制血小板的激活和聚集。
