Potential miRNA biomarkers and therapeutic targets for early atherosclerotic lesions

Abstract

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.

MicroRNAs Associated with Metformin Treatment in the Diabetes Prevention Program

“…MiRMiR-92a-3p was downregulated in the metformin group versus placebo, and our study is describing miR-92a-3p for the first time in relation to metformin response. Upregulated in fibrous plaques of early-stage atherosclerotic lesions [ 56 ]. Like miR-320a-3p, miR-92a-3p has been associated with diabetic retinopathy [ 52 ].…”

Recent Advances in Extracellular Vesicles in Amyotrophic Lateral Sclerosis and Emergent Perspectives

“…Apoptotic signaling in cancer [265] downregulated: blood plasma-derived EVs [145] miR-7975 MTDH Possible involvement in atherosclerosis [266], in lung inflammation, and cancer [267,268] upregulated: serum of sALS patients [155] miR-7977 CD84, MRPS12, MRPL27, MUC19, TRAPPC2, SIRT3, Hyppo-YAP signaling…”

From Inflammation to Oncogenesis: Tracing Serum DCLK1 and miRNA Signatures in Chronic Liver Diseases

“…This led us to investigate the correlation between DCLK1 and stage-specific transformation from liver fibrosis, cirrhosis, and HCC in patients, when compared with normal healthy subjects. While blood-based miRNAs and proteins may serve as biomarkers, they may also be used to identify potential therapeutic targets [ 30 ]. Here, we describe differentially expressed miRNAs in liver disease, the expression of some correlated with DCLK1 expression levels, and represent potential therapeutic targets for liver disease.…”