Abstract 15507: Inhibition of MEF2A Using 3rd Generation Antisense Enhances Neovascularization via Posttranscriptional Regulation of 14q32 MicroRNAs miR-329 and miR-494

Introduction and Hypothesis: The 14q32 locus encodes 54 individual microRNAs. Inhibition of 14q32 microRNAs leads to improved blood flow recovery after ischemia. Snyder et al (Development 2013) showed that transcription factor Myocyte Enhancer Factor 2A (MEF2A) induces expression of 14q32 microRNAs. Therefore, we hypothesized that inhibition of MEF2A leads to decreased 14q32 microRNA expression and thus to increased blood flow recovery after ischemia. Methods: We inhibited expression of MEF2A in a hindlimb ischemia model in mice using 3rd Generation Antisense (3GA) and studied effects on blood flow recovery, as well as on 14q32 microRNA expression. Results: Treatment with 3GA-MEF2A improved blood flow recovery within 3 days (44% recovery versus 25% recovery in control) and persisted until 14 days after induction of ischemia (80% recovery versus 60% recovery in control). However, we found no evidence of transcriptional regulation of 14q32 microRNAs. Inhibition of MEF2A decreased expression of miR-329 (p=0....