de Los Reyes-García Ascensión M, Rivera-Caravaca José Miguel, Zapata-Martínez Laura, Águila Sonia, Véliz-Martínez Andrea, García-Barberá Nuria, Gil-Perez Pablo, Guijarro-Carrillo Pedro J, Orenes-Piñero Esteban, López-García Cecilia, Lozano María L, Marín Francisco, Martínez Constantino, González-Conejero Rocío
Servicio de Hematología y Oncología Médica, Hospital General Universitario Morales Meseguer, Centro Regional de Hemodonación, Instituto Murciano de Investigación Biosanitaria (IMIB-Arrixaca), 30003 Murcia, Spain.
Servicio de Cardiología, Hospital Clínico Universitario Virgen de la Arrixaca, Universidad de Murcia, IMIB-Arrixaca, CIBERCV, 30003 Murcia, Spain.
J Pers Med. 2022 Jul 20;12(7):1185. doi: 10.3390/jpm12071185.
Studies on older patients have established notable conceptual changes in the etiopathogenesis of acute coronary syndrome (ACS), but little is known about this disease in young patients (<45 years). Of special interest is thromboinflammation, key at onset, evolution and therapy of cardiovascular pathology. Therefore, we explored whether ACS at an early age is a thromboinflammatory disease by analyzing NETs and rs2431697 of miR-146a (a miRNA considered as a brake of TLR/NF-kB pathway), elements previously related to higher rates of recurrence in atrial fibrillation and sepsis. We included 359 ACS patients (<45 years) and classified them for specific analysis into G1 (collected during the hospitalization of the first event), G2 and G3 (retrospectively collected from patients with or without ACS recurrence, respectively). cfDNA and citH3−DNA were quantified, and rs2431697 was genotyped. Analysis in the overall cohort showed a moderate but significant correlation between cfDNA and citH3−DNA and Killip−Kimball score. In addition, patients with citH3−DNA > Q4 more frequently had a history of previous stroke (6.1% vs. 1.6%). In turn, rs2431697 did not confer increased risk for the onset of ACS, but T carriers had significantly higher levels of NET markers. By groups, we found that cfDNA levels were similarly higher in all patients, but citH3−DNA was especially higher in G1, suggesting that in plasma, this marker may be attenuated over time. Finally, patients from G2 with the worst markers (cfDNA and citH3−DNA > Q2 and T allele) had a two-fold increased risk of a new ischemic event at 2-year follow-up. In conclusion, our data confirm that ACS is younger onset with thromboinflammatory disease. In addition, these data consolidate rs2431697 as a silent proinflammatory factor predisposing to NETosis, and to a higher rate of adverse events in different cardiovascular diseases.
针对老年患者的研究已证实急性冠状动脉综合征（ACS）的病因发病机制存在显著的概念性变化，但对于年轻患者（<45岁）的这种疾病却知之甚少。特别值得关注的是血栓炎症，它是心血管疾病发病、发展及治疗的关键因素。因此，我们通过分析中性粒细胞胞外诱捕网（NETs）和miR-146a的rs2431697（一种被认为是Toll样受体/核因子κB通路制动器的微小RNA），探讨早期ACS是否为血栓炎症性疾病，这些因素先前与心房颤动和脓毒症的较高复发率相关。我们纳入了359例<45岁的ACS患者，并将他们分为G1组（在首次事件住院期间采集）、G2组和G3组（分别从有或无ACS复发的患者中回顾性采集）。对游离DNA（cfDNA）和瓜氨酸化组蛋白H3-DNA（citH3−DNA）进行定量，并对rs2431697进行基因分型。对整个队列的分析显示，cfDNA与citH3−DNA以及Killip-Kimball评分之间存在中度但显著的相关性。此外，citH3−DNA>四分位数4（Q4）的患者既往有中风病史的频率更高（6.1%对1.6%）。相应地，rs2431697并未增加ACS发病的风险，但携带T等位基因者的NET标志物水平显著更高。按组分析，我们发现所有患者的cfDNA水平均同样较高，但citH3−DNA在G1组中尤其更高，这表明在血浆中，该标志物可能会随时间衰减。最后，G2组中标志物最差（cfDNA和citH3−DNA>四分位数2（Q2）且为T等位基因）的患者在2年随访时发生新的缺血性事件的风险增加了两倍。总之，我们的数据证实ACS在年轻时发病属于血栓炎症性疾病。此外，这些数据巩固了rs2431697作为一种沉默的促炎因子的地位，它易引发NETosis，并导致不同心血管疾病中不良事件的发生率更高。
