Abstract 504: MicroRNA Signatures in Murine Aorta and Carotid Arteries

Abstract

Atherosclerosis, a major cause of mortality, affects arteries diffusely. However, some vascular beds are preferably involved. In the last decade microRNAs (miRs) have emerged as key regulators of gene expression in physiological or pathophysiological processes. Here, we investigated whether different arteries, commonly affected by atherosclerosis, present specific miR expression signatures. For this purpose, aorta (Ao) and carotid (Ca) arteries of four healthy male Wistar rats were dissected, total RNA was extracted with Trizol, and enriched for small RNA fraction. MicroRNAs were then sequenced using massive parallel sequencing (RNA-Seq) on Ion Torrent PGM platform. Data were analyzed using CLC Genomics Workbench software. We identified 266 mature miRs in Ao and 421 in Ca, 260 were common between arteries. Differential expression analysis (EDGE) showed increased expression (IE) of 16 miRs in Ao and reduced expression (RE) of 54 miRs in Ao, relative to Ca. The lists of differently expressed miRs were subjected to in silico functional analyzes: (1) computational target prediction, using miRWalk tool, identified 1,094 target genes for IE list and 3,574 for RE list; (2) gene-set enrichment analysis in the lists of putative target genes, using EnrichR tool, showed differences in enriched biological processes, such as response to shear stress, regulation of endothelial proliferation, smooth muscle metabolism, and response to FGF signaling (which were enriched in RE list); (3) construction of regulatory networks for differently expressed miRs, using miRnet, identified metabolic pathway components differently regulated between arteries, such as inhibition of SIRT1 and increased expression of HIF1-alpha in Ao. Taken together, our results show differences in miR signature between arteries, suggesting that specific expression profiles of miR may play a role in the vascular behavior as well as in atherosclerosis pathophysiology.