Introduction

Platelet activation by mechanical means such as shear stress exposure, is a vital driver of thrombotic risk in implantable blood-contacting devices used in the treatment of heart failure. Lipids are essential in platelets activation and have been studied following biochemical activation. However, little is known regarding lipid alterations occurring with mechanical shear-mediated platelet activation.

Methods

Here, we determined if shear-activation of platelets induced lipidome changes that differ from those associated with biochemically-mediated platelet activation. We performed high-resolution lipidomic analysis on purified platelets from four healthy human donors. For each donor, we compared the lipidome of platelets that were non-activated or activated by shear, ADP, or thrombin treatment.

Results

We found that shear activation altered cell-associated lipids and led to the release of lipids into the extracellular environment. Shear-activated platelets released 21 phospholipids and sphingomyelins at levels statistically higher than platelets activated by biochemical stimulation.

Conclusions

We conclude that shear-mediated activation of platelets alters the basal platelet lipidome. Further, these alterations differ and are unique in comparison to the lipidome of biochemically activated platelets. Many of the released phospholipids contained an arachidonic acid tail or were phosphatidylserine lipids, which have known procoagulant properties. Our findings suggest that lipids released by shear-activated platelets may contribute to altered thrombosis in patients with implanted cardiovascular therapeutic devices.

中文翻译：

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剪切介导的血小板激活伴随着血小板脂质释放的独特改变

介绍

通过机械方式（例如剪切应力暴露）激活血小板是用于治疗心力衰竭的植入式血液接触装置中血栓形成风险的重要驱动因素。脂质对于血小板活化至关重要，并且已在生化活化后进行了研究。然而，对于机械剪切介导的血小板活化发生的脂质改变知之甚少。

方法

在这里，我们确定了血小板的剪切激活是否诱导了与生化介导的血小板激活相关的脂质组变化不同的脂质组变化。我们对四名健康人类捐赠者的纯化血小板进行了高分辨率脂质组学分析。对于每位供体，我们比较了未激活或通过剪切、ADP 或凝血酶处理激活的血小板的脂质组。

结果

我们发现剪切激活改变了细胞相关的脂质并导致脂质释放到细胞外环境中。剪切激活的血小板释放 21 种磷脂和鞘磷脂，其水平在统计学上高于生化刺激激活的血小板。

结论

我们得出结论，剪切介导的血小板激活改变了基础血小板脂质组。此外，与生化活化血小板的脂质组相比，这些改变是不同且独特的。许多释放的磷脂含有花生四烯酸尾部或磷脂酰丝氨酸脂质，它们具有已知的促凝血特性。我们的研究结果表明，剪切激活血小板释放的脂质可能有助于改变植入心血管治疗装置的患者的血栓形成。