Stratz Christian, Nührenberg Thomas, Fiebich Bernd L, Amann Michael, Kumar Asit, Binder Harald, Hoffmann Isabell, Valina Christian, Hochholzer Willibald, Trenk Dietmar, Neumann Franz-Josef
Christian Stratz, Universitäts-Herzzentrum Freiburg - Bad Krozingen, Abteilung für Kardiologie und Angiologie II, Südring 15, D-79189 Bad Krozingen, Germany, Tel.: +49 7633 4020, Fax: +49 761 4022489, E-mail:
Thromb Haemost. 2014 May 5;111(5):902-11. doi: 10.1160/TH13-06-0476. Epub 2013 Dec 19.
Diabetes mellitus as a major contributor to cardiovascular disease burden induces dysfunctional platelets. Platelets contain abundant miRNAs, which are linked to inflammatory responses and, thus, may play a role in atherogenesis. While diabetes mellitus affects plasma miRNAs, no data exist on platelet miRNA profiles in this disease. Therefore, this study sought to explore the miRNA profile of platelets in patients with diabetes mellitus that is unrelated to the presence or absence of coronary artery disease (CAD). Platelet miRNA profiles were assessed in stable diabetic and non-diabetic patients (each n=30); 15 patients in each group had CAD. Platelet miRNA was isolated from leucocyte-depleted platelet-rich plasma, and miRNA profiling was performed using LNA micro-array technology (miRBase18.0, containing 1,917 human miRNAs). Effects of diabetes mellitus were explored by univariate statistical tests for each miRNA, adjusted for potential confounders, and by developing a multivariable signature; evaluated by resampling techniques. Platelets in non-diabetic patients demonstrated miRNA expression profiles comparable to previous data. The miRNA profiles of platelets in diabetics were similar. Statistical analysis unveiled three miRNAs (miR-377-5p, miR-628-3p, miR-3137) with high reselection probabilities in resampling techniques, corresponding to signatures with modest discriminatory performance. Functional annotation of predicted targets for these miRNAs pointed towards an influence of diabetes mellitus on mRNA processing. We did not find major differences in platelet miRNA profiles between diabetics and non-diabetics. Minor differences pertained to miRNAs associated with mRNA processing. Thus, described differences in plasma miRNAs between diabetic and non-diabetic patients cannot be explained by plain changes in platelet miRNA profile.
糖尿病作为心血管疾病负担的主要促成因素,会导致血小板功能失调。血小板含有丰富的微小RNA(miRNA),这些miRNA与炎症反应相关,因此可能在动脉粥样硬化形成中发挥作用。虽然糖尿病会影响血浆miRNA,但关于该疾病中血小板miRNA谱的数据尚不存在。因此,本研究旨在探索与冠状动脉疾病(CAD)的有无无关的糖尿病患者血小板的miRNA谱。在稳定的糖尿病患者和非糖尿病患者(每组n = 30)中评估血小板miRNA谱;每组15名患者患有CAD。从去除白细胞的富含血小板血浆中分离血小板miRNA,并使用锁核酸微阵列技术(miRBase18.0,包含1917个人类miRNA)进行miRNA谱分析。通过对每个miRNA进行单变量统计检验(针对潜在混杂因素进行调整)以及开发多变量特征来探索糖尿病的影响;通过重采样技术进行评估。非糖尿病患者的血小板表现出与先前数据相当的miRNA表达谱。糖尿病患者血小板的miRNA谱相似。统计分析揭示了三种在重采样技术中具有高重选概率的miRNA(miR-377-5p、miR-628-3p、miR-3137),对应于具有适度区分性能的特征。这些miRNA预测靶点的功能注释表明糖尿病对mRNA加工有影响。我们未发现糖尿病患者和非糖尿病患者血小板miRNA谱的主要差异。微小差异与与mRNA加工相关的miRNA有关。因此,糖尿病患者和非糖尿病患者血浆miRNA中描述的差异不能通过血小板miRNA谱的简单变化来解释。