Internal and Emergency Medicine

, Volume 12, Issue 1, pp 13–22 | Cite as

An exploratory look at NETosis in atherosclerosis

  • Chiara MozziniEmail author
  • Ulisse Garbin
  • Anna Maria Fratta Pasini
  • Luciano Cominacini


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.


NETosis Atherosclerosis Venous thromboembolism Coronary artery disease Oxidative stress 







Nicotinamide adenine dinucleotide phosphate


Neutrophil elastase


Neutrophil extracellular traps


Nuclear erythroid-related factor 2


Reactive oxygen species


Tissue factor


Venous thromboembolism


Compliance with ethical standards

Conflict of interests


Ethical approval

The study was conducted in accordance with the ethical standards laid down in the Helsinki Declaration of 1975 and its late amendments. The local ethics committee approved the study.

Human and animal rights statement

No human nor animal data have been collected in this paper.

Informed consent



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Copyright information

© SIMI 2016

Authors and Affiliations

  • Chiara Mozzini
    • 1
    Email author
  • Ulisse Garbin
    • 1
  • Anna Maria Fratta Pasini
    • 1
  • Luciano Cominacini
    • 1
  1. 1.Section of Internal Medicine, Department of MedicineUniversity of VeronaVeronaItaly

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