Prof. Alessandro Weisz, MD, Laboratory of Molecular Medicine and Genomics, University of Salerno, via S. Allende, 1, 84081 Baronissi (SA), Italy, Tel.: +39 089 965043, Fax: +39 089 969657, E-mail:
Prof. Paolo Golino, MD, Department of Cardiothoracic and Respiratory Sciences, Second University of Naples, Via L. Bianchi, 1, 80131 Naples, Italy, Tel.: +39 0823 306395, Fax: +39 0823 232395, E-mail:
Thromb Haemost. 2015 Jul;114(1):96-108. doi: 10.1160/TH14-09-0726. Epub 2015 Apr 23.
Platelets carry megakaryocyte-derived mRNAs whose translation efficiency before and during activation is not known, although this can greatly affect platelet functions, both under basal conditions and in response to physiological and pathological stimuli, such as those involved in acute coronary syndromes. Aim of the present study was to determine whether changes in microRNA (miRNA) expression occur in response to activating stimuli and whether this affects activity and composition of platelet transcriptome and proteome. Purified platelet-rich plasmas from healthy volunteers were collected and activated with ADP, collagen, or thrombin receptor activating peptide. Transcriptome analysis by RNA-Seq revealed that platelet transcriptome remained largely unaffected within the first 2 hours of stimulation. In contrast, quantitative proteomics showed that almost half of > 700 proteins quantified were modulated under the same conditions. Global miRNA analysis indicated that reorganisation of platelet proteome occurring during activation reflected changes in mature miRNA expression, which therefore, appears to be the main driver of the observed discrepancy between transcriptome and proteome changes. Platelet functions significantly affected by modulated miRNAs include, among others, the integrin/cytoskeletal, coagulation and inflammatory-immune response pathways. These results demonstrate a significant reprogramming of the platelet miRNome during activation, with consequent significant changes in platelet proteome and provide for the first time substantial evidence that fine-tuning of resident mRNA translation by miRNAs is a key event in platelet pathophysiology.
血小板携带巨核细胞衍生的 mRNA，其在激活前后的翻译效率尚不清楚，尽管这可能极大地影响血小板的功能，无论是在基础条件下还是在生理和病理刺激（如急性冠脉综合征涉及的刺激）下。本研究的目的是确定 miRNA（microRNA）表达是否会因激活刺激而发生变化，以及这是否会影响血小板转录组和蛋白质组的活性和组成。从健康志愿者中采集富含血小板的血浆并使用 ADP、胶原或血栓素受体激活肽进行激活。通过 RNA-Seq 进行的转录组分析表明，在刺激的最初 2 小时内血小板转录组基本保持不变。相比之下，定量蛋白质组学表明，在相同条件下，超过 700 种定量蛋白质中的近一半被调节。全局 miRNA 分析表明，激活过程中血小板蛋白质组的重新组织反映了成熟 miRNA 表达的变化，因此，这似乎是观察到转录组和蛋白质组变化之间差异的主要驱动因素。受调节 miRNA 显著影响的血小板功能包括整合素/细胞骨架、凝血和炎症免疫反应途径等。这些结果表明，在激活过程中血小板的 miRNA 组发生了显著的重新编程，随后血小板蛋白质组发生了显著变化，并首次提供了实质性证据，表明 miRNA 对驻留 mRNA 翻译的精细调节是血小板病理生理学中的关键事件。
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