Drug-target network in myocardial infarction reveals multiple side effects of unrelated drugs

Sci Rep. 2011:1:52. doi: 10.1038/srep00052. Epub 2011 Aug 2.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cardiotonic Agents / adverse effects*
  • Cardiotonic Agents / pharmacokinetics*
  • Cardiotonic Agents / therapeutic use
  • Computer Simulation
  • Drug-Related Side Effects and Adverse Reactions / chemically induced*
  • Drug-Related Side Effects and Adverse Reactions / metabolism*
  • Humans
  • Models, Cardiovascular*
  • Myocardial Infarction / drug therapy*
  • Myocardial Infarction / metabolism*

Substances

  • Cardiotonic Agents