Transcriptomic signatures of atheroresistance in the human atrium and ventricle highlight potential candidates for targeted atherosclerosis therapeutics

Abstract

Atherosclerosis risk is not uniform throughout the cardiovascular system. This study therefore aimed to compare the transcriptomes of atheroresistant human atrium and ventricle with atheroprone coronary arteries to identify transcriptomic signatures of atheroresistance and potential targets for atherosclerosis therapeutics. Using publicly available gene read counts, differentially expressed genes between the atrium, ventricle, and coronary artery were identified for each contrast and validated against the Swiss Institute of Bioinformatics’ Bgee database. Over-representation analysis and active-subnetwork-oriented enrichment assessment then identified enriched terms, which were grouped into endothelial dysfunction-related processes. Potential biological significance was further explored with pathway analysis. Among 21474 features, 12656 differentially expressed genes were identified across the three contrasts and associated with 1215 enriched terms. There were 315 down-regulated and 133 up-regulated genes associated with endothelial dysfunction-related processes across the contrasts, including immune modulators, cell adhesion molecules, and lipid metabolism- and coagulation-related molecules. Differentially expressed genes were associated with six down-regulated Kyoto Encyclopedia of Genes and Genomes pathways, related to immune cell and associated endothelium functions. Review of regulated genes associated with endothelial dysfunction-related processes and included in these pathways, indicate immune cell-associated B cell scaffold protein with ankyrin repeats 1, as well as arterial endothelial cell-associated vascular cell adhesion molecule 1 and cadherin 5, as potential atherosclerosis targets.