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Table 2 Studies evaluating NETs biomarkers in CAD

From: Clinical significance of neutrophil extracellular traps biomarkers in thrombosis

First author/year

Study design

Included patients

Groups (No. patients)

Samples processing

NETs biomarkers

Analytical methods for NETs biomarkers

Detailed values

Antonatos et al

(2006) [69]

Case–control and cohort

Patients with acute MI and underwent thrombolysis with reteplase within 6 h from onset of pain

Acute MI (n = 13) vs. HC (n = 30)

Plasma, 800 × g and 16,000 × g

DNA

qPCR

6873 vs. 4112 GE/mL

Shimony et al

(2010) [70]

Case–control

Patients with acute STEMI

STEMI (n = 16) vs. HC (n = 47)

Serum

DNA

Sybr Gold fluorimetry

747 vs. 471 ng/mL

Borissoff et al

(2013) [71]

Case–control and cohort

Patients with chest discomfort symptoms, suspected for CAD

Extremely calcified (n = 37) vs. Severe CAD (n = 45) vs. Moderate CAD (n = 74) vs. Mild CAD (n = 75) vs. No CAD (n = 51)

Plasma, 2000 × g, 15 min, 11,000 × g, 10 min

MPO-DNA

ELISA

NA

Nucleosomes

ELISA

NA

DNA

SytoxGreen fluorimetry

79.37 (Extremely calcified) vs. 69.59 (Severe CAD) vs. 50.09 (No CAD) ng/mL

Cui et al

(2013) [72]

Case–control

Patients with ACS and SA controls

ACS (n = 137) vs. SA (n = 13) vs. HC (n = 45)

Plasma, 25 °C, 1600 × g, 10 min, 16,000 × g, 1 min

DNA

Alu sequence-based bDNA assay

2285.0 vs. 202.3 vs. 118.3 ng/mL

Ramirez et al

(2016) [79]

Case–control

Patients with STEMI underwent PCI within 1–6 h from the onset of chest pain and chronic SA controls

STEMI vs. Chronic SA vs. HC

Plasma, 4 °C, 320 × g, 15 min, 100,000 × g, 5 min

H4Cit

ELISA

NA

MPO-DNA

ELISA

NA

Langseth et al

(2018) [73]

Cohort

Patients with angiographically verified CAD, on aspirin monotherapy for at least 1 w

Clinical endpoint (n = 402) vs. No clinical endpoints (n = 394)

Serum, 2500 × g, 10 min

MPO-DNA

ELISA

NA

DNA

PicoGreen fluorimetry

402 vs. 394 ng/mL

Helseth et al

(2019) [74]

Cohort

Patients with first-time STEMI within 6 h of symptom onset admitted for PCI

Before PCI (n = 259) vs. After PCI vs. (n = 258) vs. After PCI 1 d (n = 251/254) vs. After PCI 4 m (n = 258)

Serum, 2500 × g, 10 min

MPO-DNA

ELISA

NA

DNA

PicoGreen fluorimetry

NA

Lim et al

(2019) [75]

Case–control

Patients with newly diagnosed ACS or AIS

ACS (n = 37) vs. AIS (n = 58) vs. HC (n = 25)

Plasma, 1600 × g, 15 min

DNA-histone

ELISA

19.73 vs. 13.71 vs. 14.32 mU

DNA

PicoGreen fluorimetry

743.28 vs. 524.22 vs. 216.48 ng/mL

Liu et al

(2019) [76]

Cohort

Patient was enrolled within 12 h of the onset of clinical signs and had STEMI with TIMI flow 0 before emergent PCI

Infarct-related artery (n = 36) vs. Peripheral arteries (n = 36)

Plasma

MPO-DNA

ELISA

0.44 vs. 0.28

DNA

SytoxGreen fluorimetry

0.41 vs.0.31 µg/mL

Hofbauer et al

(2019) [77]

Cohort and case–control

Patients with STEMI undergoing primary PCI for a coronary TIMI flow of 0

Culprit site (n = 48) vs. Femoral site (n = 48) vs. HC (n = 21)

Plasma, 1000 × g, 10 min

H3Cit

ELISA

332 vs. 235 vs. 192 ng/mL

DNA

PicoGreen fluorimetry

529 vs. 404 vs. 291 ng/mL

Langseth et al

(2020) [78]

Cohort

Patients diagnosed with STEMI admitted for PCI

Anterior MI (n = 413) vs. Other locations of infraction (n = 543)

Serum, 2500 × g, 10 min

H3Cit

ELISA

9.71 vs. 8.69 ng/mL

MPO-DNA

ELISA

0.188 vs. 0.171 OD

DNA

PicoGreen fluorimetry

424 vs. 409 ng/mL

Hally et al

(2021) [80]

Case–control

Patients diagnosed with MACE post-AMI within 1-year follow-up period

MACE (n = 100) vs. No MACE (n = 200)

Serum, 1500 × g, 12 min

MPO-DNA

ELISA

5.09 vs. 4.67 (% of NETs standard)

NE-DNA

ELISA

2.05 vs. 1.97 (% of pooled serum standard)

H3Cit

ELISA

7.07 vs. 5.44 (% of NETs standard)

  1. Abbreviations: ACS Acute coronary syndrome, AIS Acute ischemic stroke, AMI Acute myocardial infarction, CAD Coronary artery disease, D Day, ELISA Enzyme-linked immunosorbent assay, H Hour, H3Cit Citrullinated histone H3, HC Healthy control, M Month, MACE Major adverse cardiovascular events, MI Myocardial infarction, Min Minute, MPO Myeloperoxidase, NA Not available, NE Neutrophil elastase, NETs Neutrophil extracellular traps, OD Optical density, PCI Percutaneous coronary intervention, qPCR Quantitative polymerase chain reaction, SA Stable angina, STEMI ST-segment elevation myocardial infarction, TIMI Thrombolysis in myocardial infarction, W Week