Coronary Neutrophil Extracellular Trap Burden and DNase Activity in ST-Elevation Acute Coronary Syndrome are Predictors of ST-Segment Resolution and Infarct Size
Rationale: Mechanisms of coronary occlusion in ST-elevation acute coronary syndrome (STE-ACS) are poorly understood. We have previously reported that neutrophil (polymorphonuclear cells [PMNs]) accumulation in culprit lesion site (CLS) thrombus is a predictor of cardiovascular outcomes.
Objective: The goal of the present study was to characterize PMN activation at the CLS. We examined the relationships between CLS neutrophil extracellular traps (NETs), bacterial components as triggers of NETosis, activity of endogenous deoxyribonuclease (DNase), ST-segment resolution (STR), and infarct size.
Methods and Results: We analyzed coronary thrombectomies from 111 STE-ACS patients undergoing primary percutaneous coronary intervention. Thrombi were characterized by immunostaining, flow cytometry, bacterial profiling, immunometric and enzymatic assays. Compared to femoral PMNs, CLS PMNs were highly activated and formed aggregates with platelets. Nucleosomes, double-stranded DNA (dsDNA), neutrophil elastase, myeloperoxidase and myeloid-related protein 8/14 were increased in CLS plasma, and NETs contributed to the scaffolds of particulate coronary thrombi. Copy numbers of Streptococcus species correlated positively with amount of dsDNA. Thrombus NET burden correlated positively with infarct size and negatively with STR, while CLS DNase activity correlated negatively with infarct size and positively with STR. Recombinant DNase accelerated lysis of coronary thrombi ex vivo.
Conclusions: PMNs are highly activated in STE-ACS and undergo NETosis at the CLS. Coronary NET burden and DNase activity are predictors of STR and myocardial infarct size.
- coronary thrombus
- neutrophil extracellular traps
- plaque rupture
- polymorphonuclear neutrophils activation blood cells
- acute myocardial infarction
- thrombus aspiration
- Received August 3, 2014.
- Revision received December 24, 2014.
- Accepted December 29, 2014.