Whole Blood Transcriptomics Differentiates Circulating Gene Expression Between Coronary Artery Disease and Peripheral Artery Disease

Coronary artery disease (CAD) and peripheral artery disease (PAD) are prevalent atherosclerotic disorders that exhibit distinct clinical and pathological presentations. We used whole-blood RNA sequencing to investigate circulating transcriptomic differences between PAD and CAD. Whole-blood RNA sequencing was performed in 71 subjects 40-65 years of age with symptomatic PAD (n=20) or CAD (n=51). Patients with concomitant PAD and CAD were excluded. Differential expression analysis was performed to compare circulating gene expression in patients with PAD and patients with CAD. We identified 106 genes differentially expressed between PAD and CAD (p adj. < 0.1). Pathway analysis identified upregulation of interferon signaling pathways in CAD and upregulation of neutrophil degranulation and toll-like receptor signaling pathways in PAD. Cell type deconvolution revealed greater fractional abundance of T cell subsets in CAD compared to PAD. Patients with PAD had higher neutrophil-lymphocyte ratio that patients with CAD (3.4 vs. 2.3, p=0.01). In conclusion, PAD and CAD have unique circulating transcriptomes characterized by differences in inflammatory gene expression.