Contemporary Lifestyle and Neutrophil Extracellular Traps: An Emerging Link in Atherosclerosis Disease

Abstract

Neutrophil extracellular traps (NETs) are networks of extracellular genetic material decorated with proteins of nuclear, granular and cytosolic origin that activated neutrophils expel under pathogenic inflammatory conditions. NETs are part of the host’s innate immune defense system against invading pathogens. Interestingly, these extracellular structures can also be released in response to sterile inflammatory stimuli (e.g., shear stress, lipidic molecules, pro-thrombotic factors, aggregated platelets, or pro-inflammatory cytokines), as in atherosclerosis disease. Indeed, NETs have been identified in the intimal surface of diseased arteries under cardiovascular disease conditions, where they sustain inflammation via NET-mediated cell-adhesion mechanisms and promote cellular dysfunction and tissue damage via NET-associated cytotoxicity. This review will focus on (1) the active role of neutrophils and NETs as underestimated players of the inflammatory process during atherogenesis and lesion progression; (2) how these extracellular structures communicate with the main cell types present in the atherosclerotic lesion in the arterial wall; and (3) how these neutrophil effector functions interplay with lifestyle-derived risk factors such as an unbalanced diet, physical inactivity, smoking or lack of sleep quality, which represent major elements in the development of cardiovascular disease.