Genes Differentially Expressed Across Major Arteries Are Enriched in Endothelial Dysfunction-Related Gene Sets:...

Area of Science:

• Vascular Biology
• Genomics
• Bioinformatics

Background:

• Atherosclerosis manifests differently across major arteries, with underlying genetic factors poorly understood.
• Limited evidence suggests genetic variations contribute to artery-specific disease susceptibility.

Purpose of the Study:

• Identify differentially expressed genes (DEGs) between coronary, aortic, and tibial arteries.
• Investigate the enrichment of these DEGs in gene sets related to endothelial dysfunction.

Main Methods:

• Bioinformatic analysis of publicly available gene expression data.
• Differential gene expression analysis using DeSeq2 (FDR < 0.05).
• Over-representation and active-subnetwork enrichment analyses (FDR < 0.005).

Main Results:

• Transcriptomic differences were observed between coronary/tibial and aorta/tibial arteries, with milder changes between coronary/aorta.
• DEGs were enriched in immunity/inflammation, membrane biology, lipid metabolism, and coagulation pathways.
• Upregulation of DEGs was prevalent in coronary/tibial and aorta/tibial comparisons.

Conclusions:

• Coronary and aortic arteries exhibit distinct transcriptomic profiles compared to tibial arteries.
• These differences, particularly in immune, lipid, and coagulation pathways, suggest an atheroprone environment in the aorta and coronary arteries.
• Findings may explain the differential risk of atherosclerosis observed among major arteries.