Abstract
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.
Highlights
Heart failure (HF) is a major cause of mortality in occidental countries that is difficult to predict in clinical practice [1]
We can observe that the miRNA’s targets are involved in pathways involved in left ventricle remodeling (LVR) development such as fibroblast proliferation, regulation of reactive oxygen species metabolism and intrinsic apoptotic signaling pathways, and embryonic heart development as embryonic heart tube development and aorta development (Figure 3B). These results indicate the involvement of the 7 miRNAs in cardiac development and LVR processes
We described two systems biology analyses integrating both omics data to identify candidate miRNAs associated with LVR after myocardial infarction (MI) and to predict HF
Summary
Heart failure (HF) is a major cause of mortality in occidental countries that is difficult to predict in clinical practice [1]. LVR is characterized by cardiac hypertrophy and reduction of LV wall. LVR is an adaptive response early after MI, it is becoming deleterious in the long term [4]. Deciphering molecular events underlying LVR may offer new opportunities in the identification of early predictive biomarkers of LVR and HF. Systems biology opened new opportunities to better understand molecular networks and identify new targets involved in HF [5,6]. Among those potential targets, microRNAs (miRNAs) are non-coding RNAs of 19 to 23 nucleotides that regulate gene expression by targeting messenger RNAs [7]. ULVsiRn.gUthsienQg iathgeenQ’siaIgnegne’ns uIintgyePnautihtywaPyatkhwnoawy ledge basek, nwoewbleudiglteabapsreo, tweienb-muilitRaNpAroitneitne-rmaciRtiNonAninettewraocrtkionhingehtwligohrktihniggh1l3igchatnindgid13atceanmdiiRdaNteAms iwRNhiAchs were priorwithizicehdwtoeriedperniotirfiytizceadntdoididaetnetimfyiRcaNndAids attoedmeitReNctALsVtRo daeftteecrtMLVIR(FaifgteurreM1I)(.Figure 1)
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