Abstract P124: Human Small Artery MicroRNA Expression Profiles: Changes in Type 2 Diabetes and Associations with Endothelial Function

Background: Studies of experimental models and human blood samples support an important role of microRNAs (miRNAs) in the development of vascular dysfunction in hypertension and diabetes mellitus (DM). Information on miRNA expression in clinically directly relevant tissues such as human small arteries and its relationship with impaired vascular endothelial function is currently lacking. Methods and Results: 38 subjects (18 type 2 DM, 20 controls) underwent gluteal adipose pad biopsy to obtain small arteries for miRNA expression profiling by small RNA deep sequencing. In vivo conduit artery endothelial function was measured by brachial artery reactivity. In vitro microvascular endothelium dependent vasodilation was measured by videomicroscopy. Correlations between miRNA expression and measurements of endothelial function were calculated using generalized linear models. Several miRNAs correlated with measurements of vascular structure and function. Endothelium dependent vasodilation was impaired in type 2 DM subjects compared to controls based on both the vasodilatory response to peak dose acetylcholine (44±25 vs. 69±18 %, P=0.04) and by analyses of the entire acetylcholine dose-response curve. Several miRNAs were differentially expressed in small arteries from type 2 DM subjects, two of which were verified by real-time PCR. Cross-referencing the top 30 miRNAs (P Conclusions: Multiple miRNAs are differentially expressed in human small arteries in DM patients and correlated with in vivo or in vitro measurements of endothelial function, suggesting an important role of microvascular miRNAs in the development of endothelial dysfunction in humans.