Computational drug repositioning for peripheral arterial disease: Prediction of anti-inflammatory and pro-angiogenic therapeutics

Liang Hui Chu, Brian H. Annex, Aleksander S. Popel

Research output: Contribution to journalArticle

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Abstract

Peripheral arterial disease (PAD) results from atherosclerosis that leads to blocked arteries and reduced blood flow, most commonly in the arteries of the legs. PAD clinical trials to induce angiogenesis to improve blood flow conducted in the last decade have not succeeded. We have recently constructed PADPIN, protein-protein interaction network (PIN) of PAD, and here we combine it with the drug-target relations to identify potential drug targets for PAD. Specifically, the proteins in the PADPIN were classified as belonging to the angiome, immunome, and arteriome, characterizing the processes of angiogenesis, immune response/inflammation, and arteriogenesis, respectively. Using the network-based approach we predict the candidate drugs for repositioning that have potential applications to PAD. By compiling the drug information in two drug databases DrugBank and PharmGKB, we predict FDA-approved drugs whose targets are the proteins annotated as anti-angiogenic and pro-inflammatory, respectively. Examples of pro-angiogenic drugs are carvedilol and urokinase. Examples of anti-inflammatory drugs are ACE inhibitors and maraviroc. This is the first computational drug repositioning study for PAD.

Original languageEnglish (US)
Article number179
JournalFrontiers in Pharmacology
Volume6
Issue numberAug
DOIs
Publication statusPublished - Jan 1 2015
Externally publishedYes

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Keywords

  • Angiogenesis
  • Bioinformatics
  • Cardiovascular disease
  • Computational drug repositioning
  • Drug-target network
  • Inflammation
  • Peripheral arterial disease

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

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