Neutrophil extracellular traps and dsDNA predict outcomes among patients with ST-elevation myocardial infarction

Jing Liu,Ping Liu,Aiqun Ma,Xiqiang Wang,Tingzhong Wang,Zhonghai Zhu,Dandan Yang

doi:10.1038/s41598-019-47853-7

Abstract

Neutrophil extracellular traps (NETs) which have a potential role in noninfectious diseases, may play an important role in patients with acute coronary syndrome. The goal of this study was to investigate the association of NETs and in-hospital major adverse cardiac events among patients with ST-segment elevation myocardial infarction (STEMI). Using immunofluorescence staining, ELISA, and fluorescent enzyme standard instrument, we assessed NETs and NETs-related factors. Multivariate analyses were performed after univariate analyses to investigate which variables were independently associated with major adverse cardiac events. Compared with peripheral arteries, we observed neutrophils obtained from infarct-related artery (IRA) releasing NETs. The dsDNA levels, NET-specific marker myeloperoxidase/deoxyribonucleic acid (MPO/DNA) complexes and NETs-related factor tissue factor were significantly higher in coronary plasma samples. Multivariate analysis that white cell counts and coronary dsDNA were independently associated with in-hospital major adverse cardiac events. ROC curve for coronary dsDNA showed sensitivity of 78.0% and specificity of 53% for the cut-off value of 0.39ug/ml. Conclusion, these results provide evidences indicating NETs were associated with STIM, and occurrence of adverse cardiac events.

Highlights

Atherosclerotic plaque disruption and subsequent intraluminal thrombus formation are the primary pathological hallmark of acute myocardial infarction
This study demonstrated 4 major findings: (1) neutrophils obtained from infarct-related artery (IRA) release Neutrophil extracellular traps (NETs) (2) myeloperoxidase/deoxyribonucleic acid (MPO/DNA) and dsDNA and NETs-related factor tissue factor (TF) to be highly increased in the IRA plasma compared with peripheral artery plasma (3) conventional antithrombotics such as heparin and tirofiban was ineffective to the NETs structures. (4) coronary dsDNA is independently associated with the development of in-hospital MACEs and more sensitive than other conventional prognostic markers in patients with segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI)
Recent experimental evidence revealed the critical role of neutrophils/NETs in thrombotic events[24,25,26] and mounting evidence implicates a potential role of NETs in linking sterile inflammation with thrombosis, including atherothrombosis[7,27]

Summary

Introduction

Atherosclerotic plaque disruption and subsequent intraluminal thrombus formation are the primary pathological hallmark of acute myocardial infarction. NETs are web-like structures, comprising decondensed chromatin coated with granular proteins such as MPO and neutrophil elastase (NE)[5,6]. In patients with severe coronary atherosclerosis, plasma NETs-related structures such as dsDNA, nucleosomes, and MPO/DNA complexes are elevated. The level of nucleosomes is associated with the risk of coronary stenosis, whereas MPO/DNA complexes can predict major adverse outcomes[8]. In the blood of infarcted coronary artery, neutrophils aggregate in large numbers. It is not clear whether infarct-related coronary neutrophil released NETs or NET-related factors and their related structures are associated with adverse outcome in patients with acute STEMI. We assessed the IRA structures of NETs and their related factors www.nature.com/scientificreports/

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Conclusion