Figure 4.

Atorvastatin improves the hepatic transcriptome profile of WTD-fed APOE*3-Leiden mice. APOE*3-Leiden mice were fed a Western-type diet (WTD) with (n = 16) or without (n = 16) atorvastatin admix for 32 weeks. Chow-fed mice (n = 10) were included as a healthy reference. (A) Venn diagram illustrating the overlap of differentially expressed pathways, with the white circle representing WTD vs. chow-fed mice and the blue circle indicating atorvastatin-treated mice vs. WTD without treatment. The top 15 most significantly enriched pathways for pathways reversed by atorvastatin and the top 15 pathways solely regulated by atorvastatin are shown. (B) Upstream regulator analysis showing the predicted activation state of transcription factors/master regulators, expressed as z-score. The overlap p-value indicates significant enrichment of genes downstream of an upstream regulator and a p-value < 0.01 was considered statistically significant. Upregulation is indicated with red color and downregulation with blue color. Ranking is based on z-scores from the largest upregulation to largest downregulation by atorvastatin by category. (C) Hepatic gene expression changes in mice on WTD supplemented with atorvastatin vs. WTD alone where green color indicates decreased measurement of RNA levels and blue color indicates model-predicted inhibition.