Matches in SemOpenAlex for { <https://semopenalex.org/work/W4380786095> ?p ?o ?g. }
Showing items 1 to 86 of
86
with 100 items per page.
- W4380786095 abstract "Introduction: The identification of new treatments for atherosclerosis (ACVD), a common complex disease, is a daunting task because sets of genes, rather than individual genes, control cell functions. Using systems genetics, our team identified gene regulatory network (GRN42) that is active in the human atherosclerotic arterial wall and is involved in the regulation of foam cell formation. Hypothesis: A network-driven drug repurposing approach combined with rigorous preclinical validation will identify new uses for existing drugs to treat ACVD. Methods: We developed a GRN42-based computational drug repurposing pipeline to infer new uses for existing drugs. Selected compounds were screened by measuring their ability to inhibit foam cell formation in vitro using THP-1-derived macrophages. The in vivo efficacy was validated in ApoE-/- mice fed a western diet by histology and in atherosclerotic rabbits using histology and non-invasive 18 F-FDG PET-MR imaging. Results: 30 candidate compounds were predicted to influence the function of GRN42 and 5 were selected for in vitro screening based on their prediction scores (Figure 1A). As expected, vitamin D reduced cholesteryl esters accumulation in foam cells. Auranofin, and FDA-approved drug for rheumatoid arthritis reduced foam cell formation. As predicted methyl-fasudil had no effect, while nicardipine and flutamide increased foam cell formation (Figure 1B). Auranofin reduced plaque burden in ApoE-/- mice (Figure 1C) and in rabbits reduced lipid accumulation (Figure 1D) and inflammation shown as reduced 18 F-FDG uptake in the arterial wall (Figure 1E). Conclusions: Our results provide robust evidence that a GRN-based computational drug repurposing approach, when combined with robust preclinical validation using translational molecular imaging, can successfully identify new uses of existing drugs for the treatment of ACVD." @default.
- W4380786095 created "2023-06-16" @default.
- W4380786095 creator A5010442325 @default.
- W4380786095 creator A5012986101 @default.
- W4380786095 creator A5013411206 @default.
- W4380786095 creator A5039270409 @default.
- W4380786095 creator A5043101180 @default.
- W4380786095 creator A5043599202 @default.
- W4380786095 creator A5044800241 @default.
- W4380786095 creator A5058477900 @default.
- W4380786095 creator A5063069385 @default.
- W4380786095 creator A5063441659 @default.
- W4380786095 creator A5067811406 @default.
- W4380786095 creator A5070571941 @default.
- W4380786095 creator A5070720834 @default.
- W4380786095 creator A5074256524 @default.
- W4380786095 creator A5089434484 @default.
- W4380786095 date "2022-11-08" @default.
- W4380786095 modified "2023-10-18" @default.
- W4380786095 title "Abstract 13560: System Gene Regulatory Network-Based Drug Repurposing Combined With Preclinical Molecular Imaging Identifies Anti-Atherosclerotic Properties of Auranofin" @default.
- W4380786095 doi "https://doi.org/10.1161/circ.146.suppl_1.13560" @default.
- W4380786095 hasPublicationYear "2022" @default.
- W4380786095 type Work @default.
- W4380786095 citedByCount "0" @default.
- W4380786095 crossrefType "journal-article" @default.
- W4380786095 hasAuthorship W4380786095A5010442325 @default.
- W4380786095 hasAuthorship W4380786095A5012986101 @default.
- W4380786095 hasAuthorship W4380786095A5013411206 @default.
- W4380786095 hasAuthorship W4380786095A5039270409 @default.
- W4380786095 hasAuthorship W4380786095A5043101180 @default.
- W4380786095 hasAuthorship W4380786095A5043599202 @default.
- W4380786095 hasAuthorship W4380786095A5044800241 @default.
- W4380786095 hasAuthorship W4380786095A5058477900 @default.
- W4380786095 hasAuthorship W4380786095A5063069385 @default.
- W4380786095 hasAuthorship W4380786095A5063441659 @default.
- W4380786095 hasAuthorship W4380786095A5067811406 @default.
- W4380786095 hasAuthorship W4380786095A5070571941 @default.
- W4380786095 hasAuthorship W4380786095A5070720834 @default.
- W4380786095 hasAuthorship W4380786095A5074256524 @default.
- W4380786095 hasAuthorship W4380786095A5089434484 @default.
- W4380786095 hasConcept C103637391 @default.
- W4380786095 hasConcept C126322002 @default.
- W4380786095 hasConcept C142724271 @default.
- W4380786095 hasConcept C150903083 @default.
- W4380786095 hasConcept C207001950 @default.
- W4380786095 hasConcept C2776243873 @default.
- W4380786095 hasConcept C2777575956 @default.
- W4380786095 hasConcept C2777895019 @default.
- W4380786095 hasConcept C2778163477 @default.
- W4380786095 hasConcept C2780035454 @default.
- W4380786095 hasConcept C2780072125 @default.
- W4380786095 hasConcept C71924100 @default.
- W4380786095 hasConcept C86803240 @default.
- W4380786095 hasConcept C98274493 @default.
- W4380786095 hasConceptScore W4380786095C103637391 @default.
- W4380786095 hasConceptScore W4380786095C126322002 @default.
- W4380786095 hasConceptScore W4380786095C142724271 @default.
- W4380786095 hasConceptScore W4380786095C150903083 @default.
- W4380786095 hasConceptScore W4380786095C207001950 @default.
- W4380786095 hasConceptScore W4380786095C2776243873 @default.
- W4380786095 hasConceptScore W4380786095C2777575956 @default.
- W4380786095 hasConceptScore W4380786095C2777895019 @default.
- W4380786095 hasConceptScore W4380786095C2778163477 @default.
- W4380786095 hasConceptScore W4380786095C2780035454 @default.
- W4380786095 hasConceptScore W4380786095C2780072125 @default.
- W4380786095 hasConceptScore W4380786095C71924100 @default.
- W4380786095 hasConceptScore W4380786095C86803240 @default.
- W4380786095 hasConceptScore W4380786095C98274493 @default.
- W4380786095 hasIssue "Suppl_1" @default.
- W4380786095 hasLocation W43807860951 @default.
- W4380786095 hasOpenAccess W4380786095 @default.
- W4380786095 hasPrimaryLocation W43807860951 @default.
- W4380786095 hasRelatedWork W1987369780 @default.
- W4380786095 hasRelatedWork W2022995595 @default.
- W4380786095 hasRelatedWork W2199933705 @default.
- W4380786095 hasRelatedWork W2438771022 @default.
- W4380786095 hasRelatedWork W2913375316 @default.
- W4380786095 hasRelatedWork W3112461688 @default.
- W4380786095 hasRelatedWork W3214808407 @default.
- W4380786095 hasRelatedWork W36491935 @default.
- W4380786095 hasRelatedWork W4281768328 @default.
- W4380786095 hasRelatedWork W4376255503 @default.
- W4380786095 hasVolume "146" @default.
- W4380786095 isParatext "false" @default.
- W4380786095 isRetracted "false" @default.
- W4380786095 workType "article" @default.