Abstract 15013: The Regulation of miRNAs in rHDL-Induced Rescue of Diabetes-Impaired Angiogenesis

Introduction: Diabetic vascular complications are associated with impaired hypoxia-driven angiogenesis. We recently found that reconstituted high-density lipoproteins (rHDL) rescue diabetes-impaired angiogenesis by augmenting the classical HIF-1α/VEGFA angiogenic signalling axis, however its complete mechanism is unknown. MicroRNAs (miRNAs) regulate angiogenesis and are transported within HDL to sites of injury/repair. We seek to determine if miRNAs are regulated by rHDL in diabetes-impaired angiogenesis. Methods and Results: Using a miRNA array, we identified that rHDL suppressed miR-181c, which was confirmed with RT-PCR. A miR-181c mimic strikingly suppressed VEGFA protein levels and tubulogenesis in vitro, revealing a novel anti-angiogenic role for miR-181c. Temporal miRNA levels in the ischemic tissue and in the HDL particle was tracked in diabetic mice following the induction of hindlimb ischemia. Cohorts of mice were assessed at early (6 and 24h), mid (3 and 7 days) and later (10 days) time points p...