title: Drug-target network in myocardial infarction reveals multiple side effects of unrelated drugs.
abstract: The systems-level characterization of drug-target associations in myocardial infarction (MI) has not been reported to date. We report a computational approach that combines different sources of drug and protein interaction information to assemble the myocardial infarction drug-target interactome network (My-DTome). My-DTome comprises approved and other drugs interlinked in a single, highly-connected network with modular organization. We show that approved and other drugs may both be highly connected and represent network bottlenecks. This highlights influential roles for such drugs on seemingly unrelated targets and pathways via direct and indirect interactions. My-DTome modules are associated with relevant molecular processes and pathways. We find evidence that these modules may be regulated by microRNAs with potential therapeutic roles in MI. Different drugs can jointly impact a module. We provide systemic insights into cardiovascular effects of non-cardiovascular drugs. My-DTome provides the basis for an alternative approach to investigate new targets and multidrug treatment in MI.
authors.affiliation: Laboratory of Cardiovascular Research, Public Research Centre for Health (CRP-Santé), 120 route d'Arlon, L-1150 Luxembourg, Luxembourg. Francisco.Azuaje@crp-sante.lu
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Azuaje
authors.forename: Lu
authors.initials: L
authors.lastname: Zhang
authors.forename: Yvan
authors.initials: Y
authors.lastname: Devaux
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Wagner
mesh_terms: D002316:Cardiotonic Agents / Q000009:adverse effects* / Q000493:pharmacokinetics* / Q000627:therapeutic use; D003198:Computer Simulation; D064420:Drug-Related Side Effects and Adverse Reactions / Q000139:chemically induced* / Q000378:metabolism*; D006801:Humans; D008955:Models, Cardiovascular; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000378:metabolism*
chemical_list: D002316:Cardiotonic Agents