Coronary Neutrophil Extracellular Trap Burden and Deoxyribonuclease Activity in ST-Elevation Acute Coronary Syndrome Are Predictors of ST-Segment Resolution and Infarct Size
Coronary Neutrophil Extracellular Trap Burden and Deoxyribonuclease Activity in ST-Elevation Acute Coronary Syndrome Are Predictors of ST-Segment Resolution and Infarct Size
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DOI：
10.1161/circresaha.116.304944
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发表时间：
2015-03-27
影响因子：
20.1
通讯作者：
Lang, Irene M.
中科院分区：
文献类型：
--
作者：
Mangold, Andreas;Alias, Sherin;Lang, Irene M.
理由：st段抬高急性冠脉综合征的冠状动脉闭塞机制尚不清楚。我们之前报道过中性粒细胞（多形核细胞[PMNs]）在罪魁祸首病变部位（CLS）血栓中的积累是心血管结局的预测因子。目的：本研究的目的是表征CLS中PMN的活化。我们研究了CLS中性粒细胞胞外陷阱（NETs）、作为NETosis触发器的细菌成分、内源性脱氧核糖核酸酶活性、st段分辨率和梗死面积之间的关系。方法和结果：我们分析了111例经皮冠状动脉介入治疗的st段抬高急性冠状动脉综合征患者的冠状动脉血栓切除术。通过免疫染色、流式细胞术、细菌谱、免疫和酶分析来表征血栓。与股骨PMNs相比，CLS PMNs高度活化并与血小板形成聚集体。CLS血浆中核小体、双链DNA、中性粒细胞弹性酶、髓过氧化物酶和髓系相关蛋白8/14升高，NETs对颗粒状冠状动脉血栓支架的形成有贡献。链球菌种类的拷贝数与dsDNA呈正相关。血栓NET负荷与梗死面积成正相关，与st段溶解成负相关，而CLS脱氧核糖核酸酶活性与梗死面积成负相关，与st段溶解成正相关。重组脱氧核糖核酸酶在体外加速冠状动脉血栓的溶解。结论：PMNs在st段抬高急性冠脉综合征中高度激活，并在CLS发生NETosis。冠状动脉净网负荷和脱氧核糖核酸酶活性是st段溶解和心肌梗死面积的预测因子。
Rationale: Mechanisms of coronary occlusion in ST-elevation acute coronary syndrome 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 this 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, ST-segment resolution, and infarct size.Methods and Results: We analyzed coronary thrombectomies from 111 patients with ST-elevation acute coronary syndrome undergoing primary percutaneous coronary intervention. Thrombi were characterized by immunostaining, flow cytometry, bacterial profiling, and immunometric and enzymatic assays. Compared with femoral PMNs, CLS PMNs were highly activated and formed aggregates with platelets. Nucleosomes, double-stranded DNA, 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 dsDNA. Thrombus NET burden correlated positively with infarct size and negatively with ST-segment resolution, whereas CLS deoxyribonuclease activity correlated negatively with infarct size and positively with ST-segment resolution. Recombinant deoxyribonuclease accelerated the lysis of coronary thrombi ex vivo.Conclusions: PMNs are highly activated in ST-elevation acute coronary syndrome and undergo NETosis at the CLS. Coronary NET burden and deoxyribonuclease activity are predictors of ST-segment resolution and myocardial infarct size.