Clinical observations implicate a role of eosinophils in cardiovascular diseases, because markers of eosinophils activation are elevated in atherosclerosis and thrombosis. However, their contribution to atherosclerotic plaque formation and arterial thrombosis remains unclear. In these settings, we investigated how eosinophils are recruited and activated through an interplay with platelets. Here, we provide evidence for a central importance of eosinophil-platelet interactions in atherosclerosis and thrombosis. We show that eosinophils support atherosclerotic plaque formation involving enhanced von Willebrand factor exposure on endothelial cell and augmented platelet adhesion. During arterial thrombosis, eosinophils are quickly recruited in an integrin-dependent manner and engage in interactions with platelets leading to eosinophil activation as we show by intravital calcium imaging. These direct interactions induce the formation of eosinophil extracellular traps (EETs), which are present in human thrombi and constitute a substantial part of extracellular traps in murine thrombi. EETs are decorated with the granule protein major basic protein, which causes platelet activation by eosinophils. Consequently, targeting of EETs diminished thrombus formation in vivo identifying this approach as a novel antithrombotic concept. Finally, in our clinical analysis of coronary artery thrombi we identified female patients with stent thrombosis as the population that might derive the greatest benefit from an eosinophil inhibiting strategy. In summary, eosinophils contribute to atherosclerotic plaque formation and thrombosis through an interplay with platelets, resulting in mutual activation. Therefore, eosinophils are a promising new target in the prevention and therapy of atherosclerosis and thrombosis.

中文翻译：

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嗜酸性粒细胞-血小板相互作用通过嗜酸性粒细胞胞外陷阱促进动脉粥样硬化并稳定血栓形成

临床观察表明嗜酸性粒细胞在心血管疾病中的作用，因为嗜酸性粒细胞活化的标志物在动脉粥样硬化和血栓形成中升高。然而，它们对动脉粥样硬化斑块形成和动脉血栓形成的贡献仍不清楚。在这些情况下，我们研究了嗜酸性粒细胞是如何通过与血小板的相互作用来募集和激活的。在这里，我们提供证据证明嗜酸性粒细胞-血小板相互作用在动脉粥样硬化和血栓形成中的重要性。我们表明嗜酸性粒细胞支持动脉粥样硬化斑块的形成，涉及增强血管内皮细胞上的血管性血友病因子暴露和增强的血小板粘附。在动脉血栓形成期间，正如我们通过活体钙成像显示的那样，嗜酸性粒细胞以整合素依赖性方式迅速募集并与血小板相互作用，导致嗜酸性粒细胞活化。这些直接相互作用诱导嗜酸性粒细胞胞外陷阱 (EET) 的形成，其存在于人类血栓中，并构成鼠血栓中细胞外陷阱的重要组成部分。EET 被颗粒蛋白主要碱性蛋白修饰，这会导致嗜酸性粒细胞激活血小板。因此，靶向 EET 减少了体内血栓形成，将这种方法确定为一种新的抗血栓形成概念。最后，在我们对冠状动脉血栓的临床分析中，我们将支架血栓形成的女性患者确定为可能从嗜酸性粒细胞抑制策略中获得最大益处的人群。总之，嗜酸性粒细胞通过与血小板相互作用导致动脉粥样硬化斑块形成和血栓形成，从而导致相互激活。因此，嗜酸性粒细胞是预防和治疗动脉粥样硬化和血栓形成的一个有前景的新靶点。