Identification of miRNAs as atherosclerosis biomarkers and functional role of miR-126 in atherosclerosis progression through MAPK signalling pathway

摘要

OBJECTIVE: Mounting evidence suggests the role of microRNAs (miRNAs) in regulating inflammatory responses in various vascular diseases. Inflammation is the key mechanism leading to atherosclerosis (AS) and various miRNAs are aberrantly expressed in response to AS pathophysiology. However, there are very limited studies that serve to elucidate the role of specific miRNA in in vivo or in vitro AS models. MATERIALS AND METHODS: Microarray analysis of blood plasma of apolipoprotein deficient (apoE-/-) mice was performed followed by the confirmation using qPCR. Bone marrow mononuclear cells (BMMCs), plasma, and vessel tissue were obtained from apoE-/- mice that were induced with miR-126 mimic or inhibitor. Ox-LDL-induced THP-1 macrophages served as in vitro AS model. The release of inflammatory cytokines was detected using ELISA. The regulatory effect of miR-126 on MAP3K10 was confirmed by luciferase reporter activity and immunohistochemical analyses. RESULTS: The results showed that the miR-126 exhibited a greater fold change of expression in AS mice. Further, the functional role of miR-126 in atherosclerosis pathophysiology was demonstrated both in vivo and in vitro. miR-126 reduced the cytokine release and also decreased the AS progression. miR-126 was also found to be involved in mitogen-associated protein kinase (MAPK) signaling pathway. MAP3K10 was identified to be a direct target. CONCLUSIONS: miR-126 might serve as a biomarker of AS and its over-expression might prevent the AS progression and development.