Mir-29 Contributes To Normal Endothelial Function In Healthy Human Resistance Arterioles And Restores Endothelium-Dependent Vasodilation In Type 2 Diabetes

Introduction: The role of microRNAs (miRNAs) in regulating vascular endothelial function in human resistance vessels remains largely unexplored. Early data suggest miR-29 is differentially expressed in arterioles from humans with type 2 diabetes (T2DM) compared to healthy controls. Hypothesis: miRNA-29 will regulate endothelium-dependent vasodilation of human arterioles in a nitric oxide (NO) dependent manner though miR-29 regulated proteins. Methods: We recruited 38 subjects (18 T2DM, 20 controls). Arterioles were obtained from all subjects by gluteal adipose pad biopsy. Paired vessels from each subject underwent intraluminal transfection with either anti-miR-29 or mir-29 mimic (a and b isoforms) or scrambled control. Endothelium-dependent vasodilation was measured using increasing doses of acetylcholine (Ach) and videomicroscopy. Endothelial NO synthase (eNOS) dependence was tested using L-NAME. NO in transfected vessels was measured using DAF-2DA. LYLPA1 depalmitoylates eNOS, leading to cell membrane d...