A Six-Microrna Panel Identified as a Potential Biomarker for Early-Stage Atherosclerotic Lesions

Introduction: Atherosclerosis is a progressive disease, and it’s the common cause of cardiovascular disease (CVD). CVD is the leading cause of morbidity and mortality in the US. It is important to detect early-stage asymptomatic atherosclerosis prior to progression to plaques. However, it is not feasible to obtain target tissues from humans with early-stage atherosclerosis. We tested the hypothesis that a panel of microRNAs (miRNAs) expressed in atherosclerotic lesions and expressed in plasma of the same baboons are potential biomarkers indicative of initiation and progression of atherosclerosis. Methods and Results: We used small RNA-Seq to identify miRNA expression profiles in atherosclerotic lesions and in plasma of baboons. We challenged adult baboons (n=24) with a high cholesterol, high fat (HCHF) diet for two years. After the diet challenge, common iliac arteries were harvested, fixed in 10% buffered formalin and stained with Sudan IV. We observed interesting fatty streak lesion variations, including early stage (EGES), flat (F) and raised (R) lesions, corresponding, respectively, to AHA lesion types I, II and V. We identified 45 miRNAs differentially expressed in fatty streak lesions (ES vs F=0; ES vs R =36; F vs R=9), and 43 miRNAs in plasma of the same animals (ES vs F=0; ES vs R =21; F vs R=22). Further, we observed that miR-30-5p, miR-340-5p, miR-548-5p and let-7-3p were expressed in flat lesions as well as in plasma, whereas miR-30-5p and miR-21-5p were expressed in raised lesions and in plasma. FDR < 0.05. Conclusions: We conclude that a panel of six miRNAs differentially expressed in fatty streak lesions and differentially expressed in plasma of the same animals is a potential biomarker indicative of initiation and progression of atherosclerosis in baboons. Future studies will focus on translating baboon findings to humans.