Neutrophil Extracellular Traps Affecting Cardiovascular Health in Infectious and Inflammatory Diseases

Abstract

Neutrophil extracellular traps (NETs) are web-like structures of decondensed extracellular chromatin fibers and neutrophil granule proteins released by neutrophils. NETs participate in host immune defense by entrapping pathogens. They are pro-inflammatory in function, and they act as an initiator of vascular coagulopathies by providing a platform for the attachment of various coagulatory proteins. NETs are diverse in their ability to alter physiological and pathological processes including infection and inflammation. In this review, we will summarize recent findings on the role of NETs in bacterial/viral infections associated with vascular inflammation, thrombosis, atherosclerosis and autoimmune disorders. Understanding the complex role of NETs in bridging infection and chronic inflammation as well as discussing important questions related to their contribution to pathologies outlined above may pave the way for future research on therapeutic targeting of NETs applicable to specific infections and inflammatory disorders.

Keywords: CVD; NETs; atherosclerosis; autoimmune diseases; infection; inflammation; thrombosis.

Figure 1

NETs in atherosclerosis. (Left): cross section of an atherosclerotic vessel; (Middle): pathogens associated with the induction of NETs formation; (Right): Close up atherosclerotic lesion; Neutrophils activated e.g., by bacterial and viral pathogens may undergo NETs formation thereby activating leukocytes, platelets and endothelial cells creating a pro-inflammatory milieu triggering lesion growth. Lesional NETs may be induced by pathogens or CCL7 and initiate a IL-1beta release or a Th17 response altogether driving lesion expansion. (made with biorender.com, 4 June 2001).

Figure 2

NETs-initiated thrombosis. (Left): Cross section of a thrombus occluded artery. (Middle): NETs initiators; (Right): Pathogens may activate neutrophils to form neutrophil extracellular traps (NETs) which support (immuno)thrombosis e.g., through histone-dependent platelet activation or binding to von Willebrand factor (VWF) and display of tissue factor within the NETs structure. (made with biorender.com, accessed on 4 June 2001).

Figure 3

NETs in ANCA-associated vasculitis. (Left): Cross-section of a small vessel. (Right): Pathogenesis of ANCA-associated vasculitis is multifactorial, involving numerous immune cells. B lymphocytes feature prominently as producers of ANCAs, while activated neutrophils undergo NETs formation driving tissue damage via injury to the vascular endothelium (made with biorender.com, accessed on 4 June 2001).