Identification of potential therapeutic targets and
biomarkers indicative of burden of early
atherosclerosis that occur prior to advancement to life-threatening unstable plaques is the key to eradication of CAD prevalence and incidences. We challenged 16 baboons with a high
cholesterol, high fat diet for 2 years and evaluated early-stage atherosclerotic lesions (fatty streaks, FS, and fibrous plaques, FP) in
formalin-fixed common iliac arteries (CIA). We used small
RNA sequencing to identify expressed
miRNAs in CIA and in baseline blood samples of the same animals. We found 412 expressed
miRNAs in CIA and 356 in blood samples. Eight
miRNAs (miR-7975, -486-5p, -451a, -191-5p, -148a-3p, -17-5p, -378c, and -144-3p) were differentially expressed between paired fatty streak lesion and no-lesion sites of the tissue, and 27
miRNAs (e.g., miR-92a-3p, -5001, -342-3p, miR-28-3p, -21-5p, -221-3p, 146a-5p, and -16-5p) in fibrous plaques. The expression of 14 blood
miRNAs significantly correlated with extent of lesions and the number of plaques. We identified coordinately regulated
miRNA-gene networks in which miR-17-5p and miR-146a-5p are central hubs and miR-5001 and miR-7975 are potentially novel
miRNAs associated with early
atherosclerosis. In summary, we have identified
miRNAs expressed in lesions and in blood that correlate with lesion burden and are potential therapeutic targets and
biomarkers. These findings are a first step in elucidating
miRNA regulated molecular mechanisms that underlie early
atherosclerosis in a baboon model, enabling translation of our findings to humans.