Abstract:
Despite neutrophil involvement in inflammation and tissue repair, little is understood about their inflammatory status in acute coronary syndrome (ACS) patients with poor outcomes. Hence, we investigated the potential correlation between neutrophil inflammatory markers and the prognosis of ACS patients with/without diabetes and explored whether neutrophils demonstrate a unique inflammatory phenotype in patients experiencing an adverse in-hospital outcome. The study enrolled 229 ACS patients with or without diabetes. Poor evolution was defined as either death, left ventricular ejection fraction (LVEF) <40%, Killip Class 3/4, ventricular arrhythmias, or mechanical complications. Univariate and multivariate analyses were employed to identify clinical and paraclinical factors associated with in-hospital outcomes. Neutrophils isolated from fresh blood were investigated using qPCR, Western blot, enzymatic assay, and immunofluorescence. Poor evolution post-myocardial infarction (MI) was associated with increased number, activity, and inflammatory status of neutrophils, as indicated by significant increase of Erythrocyte Sedimentation Rate (ESR), C-reactive protein (CRP), fibrinogen, interleukin-1β (IL-1β), and, interleukin-6 (IL-6). Among the patients with complicated evolution, neutrophil activity had an important prognosis value for diabetics. Neutrophils from patients with unfavorable evolution revealed a pro-inflammatory phenotype with increased expression of CCL3, IL-1β, interleukin-18 (IL-18), S100A9, intracellular cell adhesion molecule-1 (ICAM-1), matrix metalloprotease (MMP-9), of molecules essential in reactive oxygen species (ROS) production p22phox and Nox2, and increased capacity to form neutrophil extracellular traps. Inflammation is associated with adverse short-term prognosis in acute ACS, and inflammatory biomarkers exhibit greater specificity in predicting short-term outcomes in diabetics. Moreover, neutrophils from patients with unfavorable evolution exhibit distinct inflammatory patterns, suggesting that alterations in the innate immune response in this subgroup may exert detrimental effects on disease progression.
摘要:
尽管中性粒细胞参与炎症和组织修复,对预后不良的急性冠脉综合征(ACS)患者的炎症状态了解甚少.因此,我们研究了中性粒细胞炎性标志物与有/无糖尿病的ACS患者的预后之间的潜在相关性,并探讨了中性粒细胞在出现不良住院结局的患者中是否表现出独特的炎性表型.该研究纳入了229例有或没有糖尿病的ACS患者。不良进化被定义为死亡,左心室射血分数(LVEF)<40%,Killip3/4级室性心律失常,或机械性并发症。采用单变量和多变量分析来确定与院内预后相关的临床和临床旁因素。使用qPCR研究从新鲜血液中分离的中性粒细胞,蛋白质印迹,酶测定,和免疫荧光。心肌梗死(MI)后进展不良与数量增加有关,活动,和中性粒细胞的炎症状态,如红细胞沉降率(ESR)显着增加所示,C反应蛋白(CRP),纤维蛋白原,白细胞介素-1β(IL-1β),and,白细胞介素-6(IL-6)。在进化复杂的患者中,中性粒细胞活性对糖尿病患者有重要的预后价值。来自不利发展的患者的嗜中性粒细胞显示促炎表型,CCL3,IL-1β的表达增加,白细胞介素-18(IL-18),S100A9,细胞内细胞粘附分子-1(ICAM-1),基质金属蛋白酶(MMP-9),活性氧(ROS)产生p22phox和Nox2所必需的分子,并增加了形成中性粒细胞胞外陷阱的能力。炎症与急性ACS的不良短期预后相关,和炎症生物标志物在预测糖尿病患者的短期结局方面表现出更高的特异性。此外,不良演变患者的中性粒细胞表现出不同的炎症模式,提示本亚组先天免疫应答的改变可能对疾病进展产生不利影响.