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Neutrophil extracellular traps: a catalyst for atherosclerosis

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Abstract

Neutrophil extracellular traps (NETs) are network-like structures released by activated neutrophils. They consist mainly of double-stranded DNA, histones, and neutrophil granule proteins. Continuous release of NETs in response to external stimuli leads to activation of surrounding platelets and monocytes/macrophages, resulting in damage to endothelial cells (EC) and vascular smooth muscle cells (VSMC). Some clinical trials have demonstrated the association between NETs and the severity and prognosis of atherosclerosis. Furthermore, experimental findings have shed light on the molecular mechanisms by which NETs contribute to atherogenesis. NETs play a significant role in the formation of atherosclerotic plaques. This review focuses on recent advancements in the understanding of the relationship between NETs and atherosclerosis. It explores various aspects, including the formation of NETs in atherosclerosis, clinical trials investigating NET-induced atherosclerosis, the mechanisms by which NETs promote atherogenesis, and the translational implications of NETs. Ultimately, we aim to propose new research directions for the diagnosis and treatment of atherosclerosis.

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Abbreviations

NETs:

Neutrophil extracellular traps

dsDNA:

Double-stranded DNA

citH3:

Citrullinated histone H3

MPO:

Myeloperoxidase

NE:

Neutrophil elastase

ApoB:

Apolipoprotein B

LPS:

Lipopolysaccharide

PMA:

Phorbol-12 myristate-13 acetate

ox-LDL:

Oxidized low-density lipoprotein

mtDNA:

Mitochondrial DNA

C5aR1:

Complement C5a receptor 1

STAT3:

Signal transducers and activators of transcription family 3

ROS:

Reactive oxygen species

VDAC:

Voltage-dependent ion channel

cGAS:

Cyclic GMP-AMP synthesis

PAD4:

Peptidylarginine deiminase 4

Nox:

NADPH oxidase

Ang II:

Angiotensin II

ATR1:

Angiotensin type 1 receptor

PKC:

Protein kinase C

CXCL:

Chemokine (C-X-C motif) ligand

CXCR:

Chemokine (C-X-C motif) receptor

TLR:

Toll-like receptor

IRAK1/4:

Interleukin-1 receptor-associated kinase 1/4

Cl− :

Chloride ions

SGK1:

Serum- and glucose-dependent protein kinase 1

Ca2+ :

Calcium ion

Arg:

Arginine

IRGM:

Immune-related GTPase family M protein

cPLA2:

Cytosolic phospholipase A2

cfDNA:

Cell-free DNA

STEMI:

ST-segment elevation myocardial infarction

TCC:

Terminal complement complex

TXA2:

Thromboxane A2

PSGL-1:

P-selectin glycoprotein ligand-1

ICAM:

Intercellular adhesion molecule

LFA-1:

Lymphocyte function-associated antigen 1

CCL:

Chemokine (C–C motif) ligand

vWF:

Von Willebrand Factor

NLRP3:

NOD-like receptor protein 3

IL:

Interleukin

MMP:

Matrix metalloproteinase

EGFR:

Epidermal growth factor receptor

HOCI:

Hypochlorous acid

HOSCN:

Hypothiocyanous acid

TNF:

Tumor necrosis factor

MCP-1:

Monocyte chemoattractant protein-1

EC:

Endothelial cells

EC-MVs:

Endothelial-derived microvesicles

VCAM:

Vascular cell adhesion molecule

ABCA1:

ATP binding cassette transporter A1

LCAT:

Lecithin cholesterol acyltransferase

ApoA1:

Apolipoprotein A1

eNOS:

Endothelial nitric oxide synthase

TF:

Tissue factor

VSMC:

Vascular smooth muscle cells

RAGE:

Receptors for advanced glycosylation end products

sGC:

Soluble guanylyl cyclase

ETs:

Extracellular traps

tACPA:

Therapeutic anti-citrullinated protein antibody

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Acknowledgements

This work was supported by Jiangsu Provincial Health Commission Fund Project and Jiangsu Provincial Medical Youth Talent (Grant numbers [H2018004] and [QNRC2016837]). Figures were created in BioRender.com and Pymol 2.4.1 software.

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This work was supported by Jiangsu Provincial Health Commission Fund Project and Jiangsu Provincial Medical Youth Talent (Grant Numbers [H2018004] and [QNRC2016837]).

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  1. Department of Cardiology, Affiliated Hospital of Jiangsu University, Zhenjiang, China

    Yinyu Wang, Cuiping Wang & Jiayan Li

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YW contributed toward manuscript writing & editing, JL contributed toward manuscript writing & Editing, and CW contributed toward editing and final approval of manuscript. All authors read and approved the final manuscript.

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Wang, Y., Wang, C. & Li, J. Neutrophil extracellular traps: a catalyst for atherosclerosis. Mol Cell Biochem (2024). https://doi.org/10.1007/s11010-024-04931-3

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