Recent Insights into Neutrophil Extracellular Traps in Cardiovascular Diseases
Abstract
:1. Introduction
2. NET Formation in Neutrophil Activation and Death
3. Regulation of NETs Formation and Clearance
3.1. PAD4 in NETs Formation
3.2. NAPDH Oxidase-Dependent Pathways in NETs Formation
3.3. NAPDH Oxidase-Independent Pathways in NETs Formation
3.4. DNase I in NETs Clearance
4. Clinical Evidence of NETs in CVD
4.1. NETs Levels Related to Major Adverse Cardiovascular Events (MACE)
4.2. DNase I SNP in Cardiovascular Mortality
4.3. Histological Detection of NETs in Atherosclerotic Plaque
5. Evidence from Basic Research
5.1. NETs and Endothelial Cells
5.2. NETs and Macrophages
5.3. NETs and Platelets
6. Interventional Strategies on NETs
6.1. PAD4 Inhibitors
6.2. Anticoagulants
6.3. NADPH Oxidase Inhibitor
6.4. Antibiotics
6.5. Statins
6.6. Colchicine
7. Conclusions and Perspectives
Funding
Conflicts of Interest
Abbreviations
CXCR | C-X-C chemokine receptor |
CXCL | C-X-C motif chemokine ligand |
CCL | chemokine C-C motif ligand |
ROS | reactive oxygen species |
NETs | neutrophil extracellular traps |
CVD | cardiovascular disease |
ECM | extracellular matrix |
LDL | low-density lipoprotein |
MPO | myeloperoxidase |
PMA | phorbol-12-myristate-13-acetate |
IL | interleukin |
PBMC | peripheral blood mononuclear cell |
MI | myocardial infarction |
Th 17 | cells T helper 17 cells |
PAD4 | peptidyl arginine deiminase 4 |
HMGB1 | high mobility group box 1 |
NASH | non-alcoholic steatohepatitis |
MACE | major adverse cardiovascular events |
SLE | systemic lupus erythematosus |
LDLr−/− | LDL receptor knockout |
TMAs | thrombotic microangiopathies |
PSGL-1 | P-selectin glycoprotein ligand 1 |
Myd88 | myeloid differentiation primary response 88 |
RAGE | receptor for advanced glycation end-products |
CGD | chronic granulomatous disease |
IRAKs | Interleukin-1 receptor associated kinase |
MAPK | mitogen-activated protein kinase |
SK | calcium-activated small conductance potassium |
TLR | toll-like receptor |
PF4 | platelet factor 4 |
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First Author | Type of Disease | Number of Patients | Main Findings |
---|---|---|---|
Megens et al. [41] | Atherosclerosis | Not mentioned | Plaque was dissected by endarterectomy for histological analysis. By performing immunostaining for neutrophil cell surface marker CD177 and elastase, NETs were identified by colocalization of neutrophil elastase and DAPI-stained DNA in the luminal area. |
Mangold et al. [36] | ST-elevation acute coronary syndrome | 111 | Neutrophils and NETs were enriched in culprit lesion site thrombus. Thrombus NET burden positively related to infarct size, but culprit lesion site DNase activity negatively related to infarct size. |
Stakos et al. [35] | STEMI | 18 | Thrombi from the infarct-related coronary artery contained activated platelets with NETs and active tissue factor. |
Zhou et al. [38] | Stroke | 55 stroke and 35 healthy controls | Plasma levels of NETs, activated platelets were higher in the carotid lesion than that in the aortic blood. NETs decorated with phosphatidylserine served as a platform for fibrotic factor deposition and thrombin and fibrin formation. In vitro, NETs promoted endothelial cell death. |
Hofbauer et al. [39] | ST-segment elevation myocardial infarction (STEMI) | STEMI: 711 Controls: 1422 | DNase 1 Q222R SNP was present in 64 (9.0%) STEMI patients, comparable to controls. Homozygous Q222R variant was independently associated with cardiovascular and all-cause mortality after STEMI. |
Vaidya et al. [37] | Acute coronary syndrome (ACS) | 60 (40 ACS and 20 stable angina pectosis | ACS patients were featured with increased NETs and MPO in the coronary sinus. |
Hally et al. [34] | Acute myocardial infarction (AMI) | Case-control study: 100 cases vs. 200 controls | After one year of follow-up, the odds ratio for experiencing MACE was 1.94-fold for a composite of platelet count, soluble P-selectin, and all NETs markers. |
Chilingaryan et al. [40] | STEMI | 26 | By performing histological and immunohistochemical staining, NETs were present in coronary arterial thrombi, which was associated with extracellular iron and erythrocyte fragments |
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Dong, Y.; Zhang, Y.; Yang, X.; Yan, C.; Feng, Y. Recent Insights into Neutrophil Extracellular Traps in Cardiovascular Diseases. J. Clin. Med. 2022, 11, 6662. https://doi.org/10.3390/jcm11226662
Dong Y, Zhang Y, Yang X, Yan C, Feng Y. Recent Insights into Neutrophil Extracellular Traps in Cardiovascular Diseases. Journal of Clinical Medicine. 2022; 11(22):6662. https://doi.org/10.3390/jcm11226662
Chicago/Turabian StyleDong, Yuan, Yuejie Zhang, Xuanyi Yang, Cen Yan, and Yingmei Feng. 2022. "Recent Insights into Neutrophil Extracellular Traps in Cardiovascular Diseases" Journal of Clinical Medicine 11, no. 22: 6662. https://doi.org/10.3390/jcm11226662