Abstract

Atherosclerosis is a chronic multifactorial inflammatory disease with high worldwide prevalence, and has become the leading cause of death. In the present study, we analyzed global gene expression changes in the aorta of Apolipoprotein E (ApoE) null mice fed a high-fat diet by using RNA-seq. We identified a total of 280 differentially expressed genes, of which 163 genes were upregulated and 117 genes were downregulated by high-fat diet compared with normal diet. Functional clustering and gene network analysis revealed that fatty acid metabolic process is crucial for atherosclerosis. By examining of the promoter regions of differentially expressed genes, we identified four causal transcription factors. Additionally, through connectivity map (CMap) analysis, multiple compounds were identified to have anti-atherosclerotic effects due to their ability to reverse gene expression during atherosclerosis. Our study provides a valuable resource for in-depth understanding of the mechanism underlying atherosclerosis.

Highlights

  • Atherosclerosis is a chronic multifactorial inflammatory disease with high prevalence worldwide and has become the leading cause of death [1]

  • Global gene expression profile of the aorta samples from Apolipoprotein E (ApoE) null mice fedin a length), 81.3% ofhigh-fat which diet were uniquely mapped to theThe mouse

  • ApoE null mice fed a high-fat diet compared with a normal diet using RNA-seq

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Summary

Introduction

Atherosclerosis is a chronic multifactorial inflammatory disease with high prevalence worldwide and has become the leading cause of death [1]. The principal clinical manifestations of atherosclerosis are represented by coronary heart disease, cerebral stroke, and peripheral vascular disease. Atherosclerosis represents a heterogeneous group of pathological phenomena that include endothelium damage, inflammation, metabolic disorder, cell proliferation, foam cell formation, and soft inflamed atherosclerotic plaque rupture [2]. The molecular mechanisms underlying atherosclerosis remain unclear. The mouse has been a powerful model in elucidating the genetic basis of atherogenesis. More than 80 genes have been confirmed to play a role in atherosclerosis by using gene-targeted mice [3]

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