Neutrophil extracellular traps and monocyte subsets at the culprit lesion site of myocardial infarction patients.
Andreas MangoldThomas M HofbauerAnna S OndracekTyler ArtnerThomas ScherzWalter S SpeidlKonstantin A KrychtiukRoela Sadushi-KoliciJohannes JakowitschIrene M LangPublished in: Scientific reports (2019)
Neutrophils release their chromatin into the extracellular space upon activation. These web-like structures are called neutrophil extracellular traps (NETs) and have potent prothrombotic and proinflammatory properties. In ST-elevation myocardial infarction (STEMI), NETs correlate with increased infarct size. The interplay of neutrophils and monocytes impacts cardiac remodeling. Monocyte subsets are classified as classical, intermediate and non-classical monocytes. In the present study, in vitro stimulation with NETs led to an increase of intermediate monocytes and reduced expression of CX3CR1 in all subsets. Intermediate monocytes have been associated with poor outcome, while non-classical CX3CR1-positive monocytes could have reparative function after STEMI. We characterized monocyte subsets and NET markers at the culprit lesion site of STEMI patients (n = 91). NET surrogate markers were increased and correlated with larger infarct size and with fewer non-classical monocytes. Intermediate and especially non-classical monocytes were increased at the culprit site compared to the femoral site. Low CX3CR1 expression of monocytes correlated with high NET markers and increased infarct size. In this translational system, causality cannot be proven. However, our data suggest that NETs interfere with monocytic differentiation and receptor expression, presumably promoting a subset shift at the culprit lesion site. Reduced monocyte CX3CR1 expression may compromise myocardial salvage.
Keyphrases
- peripheral blood
- dendritic cells
- st elevation myocardial infarction
- percutaneous coronary intervention
- end stage renal disease
- poor prognosis
- chronic kidney disease
- ejection fraction
- acute myocardial infarction
- left ventricular
- heart failure
- newly diagnosed
- prognostic factors
- gene expression
- st segment elevation myocardial infarction
- peritoneal dialysis
- immune response
- endothelial cells
- mass spectrometry
- machine learning
- binding protein
- transcription factor
- dna methylation
- coronary artery disease
- patient reported outcomes
- long non coding rna
- acute coronary syndrome
- genome wide
- deep learning