Gene Regulatory Network-Driven Drug Repurposing Identifies Anti-Atherosclerotic Properties of Auranofin [dataset 1]

Gene-regulatory networks (GRNs) address this complexity by providing a mechanistic framework for common disease etiologies. Using system genetics, we previously identified the human arterial wall specific GRN42 as a critical regulator of foam cell formation.

In this study, we applied a GRN-driven drug repurposing method by combining transcriptional signatures resulting from the silencing of key drivers of GRN42 to drug-related gene expression profiles from the NIH LINCS Program. This analysis identified candidate compounds predicted to modulate foam cell formation. In vitro screenings of top-selected compounds confirmed the computational predictions and demonstrated the efficacy of auranofin — an FDA-approved gold salt compound for rheumatoid arthritis — in reducing foam cell formation.