Abstract 046: A Potential MicroRNA Biomarker for Atherosclerotic Lesions in Baboons

Abstract

Introduction: Cardiovascular disease is the leading cause of death in developed countries and commonly due to atherosclerosis. Atherosclerosis is a resultant of interplay of gene and environmental factors including diet. Liver is the primary target for lipid metabolism and circulatory microRNAs (miRNAs) are potential biomarkers for atherosclerosis. However, little information is available on miRNAs for early prediction and diagnosis of severity of atherosclerosis. Hypothesis: We hypothesized that peripheral blood mononuclear cell (PBMCs) miRNA(s) are potential biomarkers for atherosclerosis. We tested this by first identifying PBMCs and liver miRNAs with discordant expression in baboons with low and high serum low density-lipoprotein cholesterol (LDL-C) concentrations and then determined if the miRNAs correlated with atherosclerotic lesions in baboons fed a high fat diet for 2 years. Methods and Results: Using Next Gen methods, we sequenced PBMCs and liver small RNA libraries from baboons discordant for LDL-C concentrations (low LDL-C, n = 3; high LDL-C, n = 3); fed a high-cholesterol, high-fat (HCHF) diet for 7 weeks. We identified 47 and 27 novel baboon miRNAs, and 494 and 490 human homologues in PBMCs and in liver, respectively. Seventy-one and 30 miRNAs showed differential response to HCHF diet in PBMCs and in liver, respectively. Comparison of miRNA expression profiles from PBMCs and liver showed concordant expression for miR-221/222 family; it was down-regulated in high LDL-C baboons in response to HCHF diet. Using qRT-PCR, we quantified miR-221 abundance in PBMCs and in livers of high LDL-C baboons (n = 109) on 2-year HCHF challenge and revealed, for hepatic miR-221, a positive correlation with severity of lesions in descending aorta (Pearson correlation coefficient, r = 0.18, p = 0.05) and aortic arch (r = 0.22, p = 0.03). Conclusions: Liver miR-221 abundance is associated with extent of lesions in baboons fed a HCHF diet for 2 years and may be a biomarker for atherosclerosis.