Abstract 18084: MiR-30e Targets IGF2-Regulated Osteogenesis in Bone Marrow Derived Mesenchymal Stem Cells, Aortic Smooth Muscle Cells, and APOE-/- Mice

Objective: In atherosclerosis, activation of an osteogenic transcriptional program in de-differentiated mesenchymal-like smooth muscle cells (SMCs) contributes substantially to the initiation of aortic calcification. We found that aortic miR-30e is downregulated with age and atherosclerosis and inversely proportional to osteogenic markers. To assess the effect of miR-30e downregulation, we tested the hypothesis that miR-30e regulates osteogenic program in bone marrow derived mesenchymal stem cells (MSCs), aortic SMCs, and APOE-/- mice. Method and Results: In aortas of old (13.5 mo) and young (6 mo) wild type and APOE-/- mice (n=4-15), we found that NFYC gene and hosted miR-30e transcripts are downregulated with age and atherosclerosis while the osteogenic markers Runx2, Opn, and Igf2 are upregulated - p Conclusion: MiR-30e represses the osteogenic program in MSCs and SMCs by targeting IGF2 and drives their differentiation into different lineages. Downregulation of miR-30e in aortas with age and atherosclerosis may trigger vascular calcification.