Recent Insights into Neutrophil Extracellular Traps in Cardiovascular Diseases

Abstract

Neutrophils are primary effector cells of the innate immune system. Emerging evidence has consistently shown that activated neutrophils produce and release neutrophil extracellular traps (NETs) that play roles in immunity and non-infectious diseases. NETs are composed of DNA and proteins and serve as a structural platform for pathogen sequestration and degradation. In contrast to their protective role during pathogenic infection, NETs are pathologically involved in cardiovascular disease (CVD). In this review, we introduce the formation, release, and clearance of NETs and the regulatory mechanisms of NETs formation, followed by an overview of the clinical evidence for the involvement of NETs in CVD. Because atherosclerosis is a fundamental part of the pathogenesis of CVD, we chose to focus on the mechanisms by which NETs promote endothelial cell damage and collaborate with macrophages and platelets to accelerate plaque progression and thrombosis. Finally, we present options for clinical intervention to inhibit NETs production and release in the treatment of CVD. In conclusion, this review integrates the latest findings and provides new insights into NETs, which represent a novel biomarker and therapeutic target in clinical practice.

Role of Neutrophil Extracellular Traps in Health and Disease Pathophysiology: Recent Advancements and Future Insights

“…A recent report demonstrates circulating endothelial glycocalyx proteins syndecan-1 and hyaluronan as predictive biomarker of coronary artery lesions in KD [222]. Interestingly NETs also promote cardiovascular EC damages suggesting that enhanced NET generation may participate to the pathogenesis of KD vasculitis [223]. Again, high levels of proinflammatory mediators including TNFα, IL-1β and IL-8 have been reported in KD patients which are strong inducer of neutrophils to release NETs [22,218].…”

Spontaneous reperfusion in STEMI: Its mechanisms and possible modulation

“…NETs also enhance blood coagulation, not only by activating the intrinsic pathway of coagulation but also by degrading tissue factor pathway inhibitor, the major extrinsic coagulation pathway inhibitor. NETs can impair smooth muscle cells and the death of smooth muscle cells and foam cells, together with the degradation of the extra-cellular matrix, results in thinning of the fibrous cap and the formation of rupture-prone vulnerable plaques [59].…”

Neutrophil extracellular traps in acute coronary syndrome

“…PAD4 is a protease that catalyzes the guanylation of arginine residues and is involved in NETosis. CL-amidine, a PAD4 mimetic peptide, competitively binds to PAD4 and inhibits its action [ 68 ]. Therefore, inhibition of PAD4 by drugs such as chloro-amidine is a possible target for treating NET-related diseases.…”