Coronary artery endothelial phenotype differences related to atherosusceptibility emerge from a multi‐arterial site analysis in adult swine

Abstract

Atherosclerosis originates as focal arterial lesions having a predictable distribution to regions of disturbed blood flow. Endothelial cells (EC) play a key role in the initiation of lesions. Having previously reported a significant association of EC phenotype with the flow environment in a 3‐region comparison in vivo (Passerini et al, 2005), we extended this observation to 13 distinct coronary and non‐coronary regions (7 susceptible, 6 protected) in 87 adult swine. Site‐specific EC RNA was linearly amplified and hybridized to porcine microarrays. Hierarchical clustering, Pearson correlation calculations, and differential gene expression analyses identified a significant degree of heterogeneity of EC phenotypes as a function of site and hemodynamic environment. Most notably, we observed distinct coronary EC transcript profiles relative to non‐coronary regions. Within coronary artery athero‐susceptible regions, 262 features were differentially expressed relative to atheroprotected regions (25% false discovery rate). NIH DAVID functional annotation of these features identified protein metabolism, apoptosis, and anti‐oxidant activity as enriched themes. Gene Set Enrichment Analysis also identified 140 gene sets (out of 548) as upregulated, including inflammation and immune response, with core genes included within the DAVID results for these regions. Supported by the NHLBI.