Demyanets Svitlana, Stojkovic Stefan, Mauracher Lisa-Marie, Kopp Christoph W, Wojta Johann, Thaler Johannes, Panzer Simon, Gremmel Thomas
Department of Laboratory Medicine, Medical University of Vienna, Waehringer-Guertel 18-20, 1090 Vienna, Austria.
Department of Internal Medicine II, Medical University of Vienna, Waehringer-Guertel 18-20, 1090 Vienna, Austria.
J Clin Med. 2020 Jan 22;9(2):304. doi: 10.3390/jcm9020304.
Neutrophil extracellular traps (NETs) are supposed to play a central role in atherothrombosis. We measured circulating citrullinated histone H3 (H3Cit) and cell-free DNA (cfDNA), which serve as surrogate markers of NET formation, in 79 patients with peripheral artery disease (PAD) following infrainguinal angioplasty with stent implantation. Analysis of cfDNA and H3Cit was performed using Quant-iT™ PicoGreen dsDNA Assay Kit or an ELISA, respectively. Within two years of follow-up, the primary endpoint defined as nonfatal myocardial infarction, stroke or transient ischemic attack, cardiovascular death, and >80% target vessel restenosis occurred in 34 patients (43%). Both H3Cit (HR per 1-SD: 2.72; 95% CI: 1.2-6.3; = 0.019) and cfDNA (HR per 1-SD: 2.15; 95% CI: 1.1-4.2; = 0.028) were associated with the primary endpoint in a univariate Cox regression analysis. Multivariate linear regression analyses showed associations between cfDNA and platelet surface expression of P-selectin ( = 0.006) and activated glycoprotein IIb/IIIa ( < 0.001) in response to arachidonic acid (AA) after adjustment for age, sex, clinical risk factors, and inflammatory markers. H3Cit was also associated with P-selectin expression in response to thrombin-receptor activating peptide ( = 0.048) and AA ( = 0.032). Circulating H3Cit and cfDNA predict ischemic outcomes after peripheral angioplasty with stent implantation, and are associated with on-treatment platelet activation in stable PAD.
中性粒细胞胞外诱捕网（NETs）被认为在动脉粥样硬化血栓形成中起核心作用。我们在79例接受股下血管成形术并植入支架的外周动脉疾病（PAD）患者中，测量了作为NET形成替代标志物的循环瓜氨酸化组蛋白H3（H3Cit）和游离DNA（cfDNA）。分别使用Quant-iT™ PicoGreen双链DNA检测试剂盒或酶联免疫吸附测定法（ELISA）对cfDNA和H3Cit进行分析。在两年的随访期内，34例患者（43%）发生了定义为非致命性心肌梗死、中风或短暂性脑缺血发作、心血管死亡以及靶血管再狭窄>80%的主要终点事件。在单变量Cox回归分析中，H3Cit（每1标准差的风险比：2.72；95%置信区间：1.2 - 6.3；P = 0.019）和cfDNA（每1标准差的风险比：2.15；95%置信区间：1.1 - 4.2；P = 0.028）均与主要终点事件相关。多变量线性回归分析显示，在对年龄、性别、临床风险因素和炎症标志物进行校正后，cfDNA与花生四烯酸（AA）刺激后血小板表面P-选择素的表达（P = 0.006）以及活化糖蛋白IIb/IIIa的表达（P < 0.001）相关。H3Cit也与凝血酶受体激活肽刺激后（P = 0.048）和AA刺激后（P = 0.032）的P-选择素表达相关。循环H3Cit和cfDNA可预测支架植入外周血管成形术后的缺血性结局，并与稳定型PAD患者治疗期间的血小板活化相关。
