Pordzik Justyna, Eyileten-Postuła Ceren, Jakubik Daniel, Czajka Pamela, Nowak Anna, De Rosa Salvatore, Gąsecka Aleksandra, Cieślicka-Kapłon Agnieszka, Sulikowski Piotr, Filipiak Krzysztof J, Mirowska-Guzel Dagmara, Siller-Matula Jolanta M, Postuła Marek
Department of Experimental and Clinical Pharmacology, Centre for Preclinical Research and Technology (CEPT), Medical University of Warsaw, Banacha 1B, 02-097 Warsaw, Poland.
Division of Cardiology, Department of Medical and Surgical Sciences, "Magna Graecia" University, 88100 Catanzaro, Italy.
J Clin Med. 2021 May 28;10(11):2371. doi: 10.3390/jcm10112371.
MicroRNAs are endogenous non-coding RNAs that are involved in numerous biological processes through regulation of gene expression. The aim of our study was to determine the ability of several miRNAs to predict mortality and response to antiplatelet treatment among T2DM patients. Two hundred fifty-two patients with diabetes were enrolled in the study. Among the patients included, 26 (10.3%) patients died within a median observation time of 5.9 years. The patients were receiving either acetylsalicylic acid (ASA) 75 mg (65%), ASA 150 mg (15%) or clopidogrel (19%). Plasma miR-126, miR-223, miR-125a-3p and Let-7e expressions were assessed by quantitative real time PCR and compared between the patients who survived and those who died. Adjusted Cox-regression analysis was used for prediction of mortality. Differential miRNA expression due to different antiplatelet treatment was analyzed. After including all miRNAs into one multivariate Cox regression model, only miR-126 was predictive of future occurrence of long-term all-cause death (HR = 5.82, 95% CI: 1.3-24.9; = 0.024). Furthermore, miR-126, Let-7e and miR-223 expressions in the clopidogrel group were significantly higher than in the ASA group ( = 0.014; = 0.013; = 0.028, respectively). To conclude, miR-126 expression is a strong and independent predictor of long-term all-cause mortality among patients with T2DM. Moreover, miR-223, miR-126 and Let-7e present significant interactions with antiplatelet treatment regimens and clinical outcomes.
微小RNA是内源性非编码RNA,通过调节基因表达参与众多生物学过程。我们研究的目的是确定几种微小RNA预测2型糖尿病(T2DM)患者死亡率及抗血小板治疗反应的能力。252例糖尿病患者纳入本研究。在纳入的患者中,26例(10.3%)在中位观察时间5.9年内死亡。患者接受75mg阿司匹林(ASA)(65%)、150mg ASA(15%)或氯吡格雷(19%)治疗。通过定量实时PCR评估血浆miR-126、miR-223、miR-125a-3p和Let-7e表达,并在存活患者和死亡患者之间进行比较。采用校正Cox回归分析预测死亡率。分析不同抗血小板治疗导致的微小RNA表达差异。将所有微小RNA纳入一个多变量Cox回归模型后,只有miR-126可预测未来长期全因死亡的发生(风险比=5.82,95%可信区间:1.3 - 24.9;P = 0.024)。此外,氯吡格雷组中miR-126、Let-7e和miR-223表达显著高于ASA组(分别为P = 0.014;P = 0.013;P = 0.028)。总之,miR-126表达是T2DM患者长期全因死亡率的强大且独立预测指标。此外,miR-223、miR-126和Let-7e与抗血小板治疗方案及临床结局存在显著相互作用。