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  Eosinophil-platelet interactions promote atherosclerosis and stabilize thrombosis with eosinophil extracellular traps

Marx, C., Novotny, J., Salbeck, D., Zellner, K. R., Nicolai, L., Pekayvaz, K., et al. (2019). Eosinophil-platelet interactions promote atherosclerosis and stabilize thrombosis with eosinophil extracellular traps. BLOOD, 134(21), 1859-1872. doi:10.1182/blood.2019000518.

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 Creators:
Marx, Charlotte1, Author
Novotny, Julia1, Author
Salbeck, Danby1, Author
Zellner, Katie R.1, Author
Nicolai, Leo1, Author
Pekayvaz, Kami1, Author
Kilani, Badr1, Author
Stockhausen, Sven1, Author
Buergener, Niklas1, Author
Kupka, Danny1, Author
Stocker, Thomas J.1, Author
Weckbach, Ludwig T.1, Author
Pircher, Joachim1, Author
Moser, Markus2, Author              
Joner, Michael1, Author
Desmet, Walter1, Author
Adriaenssens, Tom1, Author
Neumann, Franz-Josef1, Author
Gerschlick, Anthony H.1, Author
ten Berg, Jurrien M.1, Author
Lorenz, Michael1, AuthorStark, Konstantin1, Author more..
Affiliations:
1external, ou_persistent22              
2Fässler, Reinhard / Molecular Medicine, Max Planck Institute of Biochemistry, Max Planck Society, ou_1565147              

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Free keywords: VON-WILLEBRAND-FACTOR; ACTIVATED PLATELETS; PERIPHERAL-BLOOD; TISSUE FACTOR; PROTEINS; ADHESION; DNA; ASSOCIATION; NEUTROPHILS; EXPRESSION
 Abstract: Clinical observations implicate a role of eosinophils in cardiovascular diseases because markers of eosinophil 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 cells 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, which identifies 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.

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Language(s): eng - English
 Dates: 2019
 Publication Status: Published in print
 Pages: 14
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Identifiers: ISI: 000499645800012
DOI: 10.1182/blood.2019000518
 Degree: -

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Title: BLOOD
Source Genre: Journal
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Publ. Info: 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA : AMER SOC HEMATOLOGY
Pages: - Volume / Issue: 134 (21) Sequence Number: - Start / End Page: 1859 - 1872 Identifier: ISSN: 0006-4971