From the Leibniz-Institut für Analytische Wissenschaften-ISAS-e.V., Dortmund, Germany (J.M.B., A.S., R.P.Z); Institut für Klinische Biochemie und Pathobiochemie, Universitätsklinikum Würzburg, Würzburg, Germany (S.G.); Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences, St. Petersburg, Russia (S.G.); Centre for Cardiovascular Sciences, Institute for Biomedical Research, College of Medical and Dental Sciences, University of Birmingham, Birmingham, United Kingdom (S.P.W.); Center for Thrombosis and Hemostasis, Universitätsklinikum der Johannes Gutenberg-Universität Mainz, Mainz, Germany (K.J., U.W.); Medizinisches Proteom Center, Ruhr Universität Bochum, Bochum, Germany (A.S.); Department of Chemistry, College of Physical Sciences, University of Aberdeen, Aberdeen, Scotland, United Kingdom (A.S.); and Department of Biochemistry, CARIM, Maastricht University, Maastricht, The Netherlands (J.W.M.H.).
Circ Res. 2014 Mar 28;114(7):1204-19. doi: 10.1161/CIRCRESAHA.114.301598.
More than 130 years ago, it was recognized that platelets are key mediators of hemostasis. Nowadays, it is established that platelets participate in additional physiological processes and contribute to the genesis and progression of cardiovascular diseases. Recent data indicate that the platelet proteome, defined as the complete set of expressed proteins, comprises >5000 proteins and is highly similar between different healthy individuals. Owing to their anucleate nature, platelets have limited protein synthesis. By implication, in patients experiencing platelet disorders, platelet (dys)function is almost completely attributable to alterations in protein expression and dynamic differences in post-translational modifications. Modern platelet proteomics approaches can reveal (1) quantitative changes in the abundance of thousands of proteins, (2) post-translational modifications, (3) protein-protein interactions, and (4) protein localization, while requiring only small blood donations in the range of a few milliliters. Consequently, platelet proteomics will represent an invaluable tool for characterizing the fundamental processes that affect platelet homeostasis and thus determine the roles of platelets in health and disease. In this article we provide a critical overview on the achievements, the current possibilities, and the future perspectives of platelet proteomics to study patients experiencing cardiovascular, inflammatory, and bleeding disorders.
130 多年前,人们就认识到血小板是止血的关键介质。如今,已经确定血小板参与了其他生理过程,并有助于心血管疾病的发生和发展。最近的数据表明,血小板蛋白质组(定义为表达蛋白的全部集合)包含超过 5000 种蛋白,并且在不同的健康个体之间非常相似。由于其无核性质,血小板的蛋白质合成能力有限。因此,在经历血小板疾病的患者中,血小板(功能)障碍几乎完全归因于蛋白表达的改变和翻译后修饰的动态差异。现代血小板蛋白质组学方法可以揭示(1)数千种蛋白丰度的定量变化,(2)翻译后修饰,(3)蛋白-蛋白相互作用,以及(4)蛋白定位,而仅需要几毫升范围内的少量血液捐献。因此,血小板蛋白质组学将成为研究心血管、炎症和出血性疾病患者的基本过程的宝贵工具,这些过程决定了血小板在健康和疾病中的作用。在本文中,我们对血小板蛋白质组学在研究经历心血管、炎症和出血性疾病的患者方面的成就、当前可能性和未来展望进行了批判性的综述。