A novel lesional transciptional signature separates atherosclerosis with and without diabetes in Yorkshire swine and humans

This study identifies evolutionarily conserved gene signatures and signaling pathways in a stage-specific manner that successfully distinguishes diabetes and non-diabetes-associated atherosclerosis. These findings establish new molecular insights and therapeutic opportunities to potentially control accelerated atherosclerotic lesion formation in diabetes. Serial 3-mm coronary artery segments of hypercholesterolemic Yorkshire swine and diabetic-hypercholesterolemic swine were characterized as mild, moderate, or severe phenotypic manifestations of coronary atherosclerosis based on histopathology. Lesional RNA-Sequencing was performed (n=3-8 lesions per group) corresponding to increasing phenotypic severity. Differentially expressed genes, transcription factors, upstream regulators, and hubs were validated using NanoString technology and a human atherosclerotic specimen cohort.