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An exploratory look at NETosis in atherosclerosis

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Abstract

Current evidence suggests the likelihood of a link between venous thromboembolism (VTE) and atherosclerosis, although they have been traditionally considered as different pathological entities. The contribution of neutrophils to human atherogenesis has been underestimated, if compared to their contribution established in VTE. This is due to the major importance attributed to macrophages in plaque destabilization. Nevertheless, the role of neutrophils in atherogenesis deserves increasing attention. In particular, neutrophil extracellular traps (NETs) are net-like chromatin fibres that are released from dying neutrophils. The death of neutrophils with NETs formation is called NETosis. During activation, neutrophils produce reactive oxygen species (ROS), through the activation of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. The main function of NETs is trapping and killing pathogens. Nevertheless, NETs formation has been observed in various chronic inflammatory diseases, autoimmune diseases, vasculitis, lung diseases, cancer and VTE. Recent studies suggest that NETs formation might contribute also to atherosclerosis progression. New data report the presence of NETs in the luminal portion of human atherosclerotic vessels and coronary specimens obtained from patients after acute myocardial infarction. Programmed death mechanisms in atherosclerosis such as apoptosis, efferocytosis and also NETosis, share common features and triggers. If defective, they can lead the cells to a switch from programmed death to necrosis, resulting in the release of pro-atherogenic factors, accumulation of cell debris and progression of the disease. This review provides evidence on the emerging role of neutrophils focusing on NETosis and oxidative stress burden in orchestrating common mechanisms in atherosclerosis and thrombosis.

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Abbreviations

MP:

Microparticles

MPO:

Myeloperoxidase

NADPH:

Nicotinamide adenine dinucleotide phosphate

NE:

Neutrophil elastase

NETs:

Neutrophil extracellular traps

Nrf2:

Nuclear erythroid-related factor 2

ROS:

Reactive oxygen species

TF:

Tissue factor

VTE:

Venous thromboembolism

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  1. Section of Internal Medicine, Department of Medicine, University of Verona, 10, Piazzale L.A. Scuro, 37134, Verona, Italy

    Chiara Mozzini, Ulisse Garbin, Anna Maria Fratta Pasini & Luciano Cominacini

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  1. Chiara Mozzini
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  2. Ulisse Garbin
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Mozzini, C., Garbin, U., Fratta Pasini, A. et al. An exploratory look at NETosis in atherosclerosis. Intern Emerg Med 12, 13–22 (2017). https://doi.org/10.1007/s11739-016-1543-2

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