Epidemiological studies show that cardiovascular events related to platelet hyperactivity remain the leading causes of death among multiple sclerosis (MS) patients. Quantitative or structural changes of platelet cytoskeleton alter their morphology and function. Here, we demonstrated, for the first time, the structural changes in MS platelets that may be related to their hyperactivity. MS platelets were found to form large aggregates compared to control platelets. In contrast to the control, the images of overactivated, irregularly shaped MS platelets show changes in the cytoskeleton architecture, fragmented microtubule rings. Furthermore, MS platelets have long and numerous pseudopodia rich in actin filaments. We showed that MS platelets and megakaryocytes, overexpress β1-tubulin and β-actin mRNAs and proteins and have altered post-translational modification patterns. Moreover, we identified two previously undisclosed mutations in the gene encoding β1-tubulin in MS. We propose that the demonstrated structural changes of platelet cytoskeleton enhance their ability to adhere, aggregate, and degranulate fueling the risk of adverse cardiovascular events in MS.

中文翻译：

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多发性硬化症（MS）中血小板细胞骨架蛋白的数量和结构变化

流行病学研究表明，与血小板过度活跃相关的心血管事件仍然是多发性硬化症（MS）患者死亡的主要原因。血小板细胞骨架的数量或结构变化改变其形态和功能。在这里，我们首次证明了 MS 血小板的结构变化可能与其过度活跃有关。与对照血小板相比，MS 血小板被发现形成大的聚集体。与对照相比，过度激活、形状不规则的 MS 血小板的图像显示细胞骨架结构的变化、微管环碎片。此外，MS 血小板具有长而大量的富含肌动蛋白丝的伪足。我们发现 MS 血小板和巨核细胞过度表达 β1-微管蛋白和 β-肌动蛋白 mRNA 和蛋白质，并改变了翻译后修饰模式。此外，我们在 MS 中的 β1-微管蛋白编码基因中发现了两个先前未公开的突变。我们认为，血小板细胞骨架的结构变化增强了其粘附、聚集和脱颗粒的能力，从而增加了多发性硬化症中不良心血管事件的风险。