Helseth Ragnhild, Knudsen Eva Cecilie, Eritsland Jan, Opstad Trine Baur, Arnesen Harald, Andersen Geir Øystein, Seljeflot Ingebjørg
Center for Clinical Heart Research, Department of Cardiology, Oslo University Hospital Ullevål, PB 4956, Nydalen, 0424, Oslo, Norway.
University of Oslo, Oslo, Norway.
BMC Cardiovasc Disord. 2019 Oct 15;19(1):221. doi: 10.1186/s12872-019-1205-1.
Neutrophil extracellular traps (NETs) have recently been identified as mediators in atherothrombosis. Although NETosis in general has been suggested to be glucose dependent, the transferability to patients with acute ST-elevation myocardial infarction (STEMI) is unclear. We assessed whether the NETs markers double-stranded deoxyribonucleid acid (dsDNA) and myeloperoxidase-DNA (MPO-DNA) associated with plasma glucose and the glucometabolic status in the acute phase and 3 months after a STEMI. We also explored whether an acute glucose load resulted in upregulated NETosis by assessment of peptidylarginine deiminase 4 (PAD4) gene expression.
In total, 224 STEMI patients were prospectively enrolled and underwent blood sampling acutely (median 16.5 h after PCI) and after 3 months. Glucometabolic status was defined based on the results of an oral glucose tolerance test (OGTT) as normal glucose regulation (NGR), impaired fasting glucose (IFG), impaired glucose tolerance (IGT) or type 2 diabetes (T2DM). dsDNA and MPO-DNA were measured in serum, while PAD4 mRNA was measured in circulating leukocytes by RT-PCR.
dsDNA levels were significantly correlated to plasma glucose both acutely and after 3 months (r = 0.12 and r = 0.17, both p < 0.02), whereas MPO-DNA was not. No associations with the glucometabolic status were encountered for dsDNA and MPO-DNA acutely, but after 3 months dsDNA levels were elevated in patients with IFG and T2DM vs. NGR (428 vs. 371 ng/ml and 408 vs. 371 ng/ml, both p < 0.045). During the acute glucose load after 3 months, dsDNA and MPO-DNA remained unchanged while PAD4 mRNA increased significantly (RQ 0.836 vs. 0.920, p = 0.02).
In this cohort of STEMI patients, levels of dsDNA associated with plasma glucose both in the acute and stable condition. The glucometabolic status was not substantially related to the selected NETs markers, however, an acute glucose load by OGTT performed after 3 months resulted in increased PAD4 expression, suggestive of enhanced NETosis in the aftermath of STEMI.
www.clinicaltrials.gov, NCT00926133 . Registered June 23, 2009.
中性粒细胞胞外诱捕网（NETs）最近被确定为动脉粥样硬化血栓形成的介质。尽管一般认为NETosis依赖葡萄糖，但在急性ST段抬高型心肌梗死（STEMI）患者中的可转移性尚不清楚。我们评估了NETs标志物双链脱氧核糖核酸（dsDNA）和髓过氧化物酶-DNA（MPO-DNA）在STEMI急性期及3个月后是否与血糖和糖代谢状态相关。我们还通过评估肽基精氨酸脱亚氨酶4（PAD4）基因表达，探讨急性葡萄糖负荷是否会导致NETosis上调。
共前瞻性纳入224例STEMI患者，在急性期（PCI后中位数16.5小时）和3个月后进行血样采集。根据口服葡萄糖耐量试验（OGTT）结果将糖代谢状态定义为正常血糖调节（NGR）、空腹血糖受损（IFG）、糖耐量受损（IGT）或2型糖尿病（T2DM）。测定血清中的dsDNA和MPO-DNA，通过逆转录聚合酶链反应（RT-PCR）测定循环白细胞中的PAD4 mRNA。
dsDNA水平在急性期和3个月后均与血糖显著相关（r分别为0.12和0.17，均p<0.02），而MPO-DNA则不然。dsDNA和MPO-DNA在急性期与糖代谢状态无关联，但3个月后，IFG和T2DM患者的dsDNA水平高于NGR患者（分别为428 vs. 371 ng/ml和408 vs. 371 ng/ml，均p<0.045）。在3个月后的急性葡萄糖负荷期间，dsDNA和MPO-DNA保持不变，而PAD4 mRNA显著增加（相对定量分别为0.836 vs. 0.920，p=0.02）。
在这组STEMI患者中，dsDNA水平在急性期和稳定期均与血糖相关。糖代谢状态与所选的NETs标志物无实质性关联，然而，3个月后进行的OGTT急性葡萄糖负荷导致PAD4表达增加，提示STEMI后NETosis增强。
