Charrier Henri, Cuvelliez Marie, Dubois-Deruy Emilie, Mulder Paul, Richard Vincent, Bauters Christophe, Pinet Florence
Inserm, Institut Pasteur de Lille, Université de Lille, FHU-REMOD-VHF, U1167-RID-AGE, F-59000 Lille, France.
Normandie University, UNIROUEN, Inserm U1096, FHU-REMOD-VHF, 7F-6000 Rouen, France.
Noncoding RNA. 2019 Mar 7;5(1):22. doi: 10.3390/ncrna5010022.
Heart failure (HF) has several etiologies including myocardial infarction (MI) and left ventricular remodeling (LVR), but its progression remains difficult to predict in clinical practice. Systems biology analyses of LVR after MI provide molecular insights into this event such as modulation of microRNA (miRNA) that could be used as a signature of HF progression. To define a miRNA signature of LVR after MI, we use 2 systems biology approaches, integrating either proteomic data generated from LV of post-MI rat induced by left coronary artery ligation or multi-omics data (proteins and non-coding RNAs) generated from plasma of post-MI patients from the REVE-2 study. The first approach predicted that 13 miRNAs and 3 of these miRNAs would be validated to be associated with LVR in vivo: miR-21-5p, miR-23a-3p and miR-222-3p. The second approach predicted that 24 miRNAs among 1310 molecules and 6 of these miRNAs would be selected to be associated with LVR in silico: miR-17-5p, miR-21-5p, miR-26b-5p, miR-222-3p, miR-335-5p and miR-375. We identified a signature of 7 microRNAs associated with LVR after MI that support the interest of integrative systems biology analyses to define a miRNA signature of HF progression.
心力衰竭（HF）有多种病因，包括心肌梗死（MI）和左心室重构（LVR），但其进展在临床实践中仍难以预测。对心肌梗死后左心室重构的系统生物学分析为这一事件提供了分子层面的见解，例如对可作为心力衰竭进展标志的微小RNA（miRNA）的调控。为了确定心肌梗死后左心室重构的miRNA特征，我们使用了两种系统生物学方法，一种是整合左冠状动脉结扎诱导的心肌梗死后大鼠左心室产生的蛋白质组学数据，另一种是整合REVE-2研究中心肌梗死后患者血浆产生的多组学数据（蛋白质和非编码RNA）。第一种方法预测了13种miRNA，其中3种miRNA在体内被验证与左心室重构相关：miR-21-5p、miR-23a-3p和miR-222-3p。第二种方法预测了1310个分子中的24种miRNA，其中6种miRNA在计算机模拟中被选择与左心室重构相关：miR-17-5p、miR-21-5p、miR-26b-5p、miR-222-3p、miR-335-5p和miR-375。我们确定了一种与心肌梗死后左心室重构相关的7种微小RNA的特征，这支持了综合系统生物学分析在定义心力衰竭进展的miRNA特征方面的价值。
