Abstract 21290: Adipose Tissue Factors and the Adipokine Resistin-Induce Vascular Endothelial Dysfunction via Arginase Upregulation

Introduction: Obesity is a major contributor to cardiovascular disorders, for which endothelial cell (EC) dysfunction is a hallmark. Obesity-induced EC dysfunction has been linked to dysregulation of the visceral adipose tissue (VAT) resulting in increased secretion of the pro-inflammatory cytokine resistin and alterations in endothelial nitric oxide (NO) producing capacity. However, mechanisms underlying this pathology are not well understood. Hypothesis: Resistin impairs vascular EC function via upregulation of endothelial arginase1 (ARG1) expression and activity, thus limiting L-arginine availability for NO synthesis. Methods: To determine the effect of obesity on EC function, conditioned media prepared from VAT (VAT CM) of high fat diet-induced obese mice, VAT CM from lean mice or resistin (100 ηg/ml) were used to treat mouse aortic endothelial cells (MAEC) and aortic rings for 24 hr. Results: VAT CM from obese mice increased endothelial ARG1 mRNA by 34% and decreased NO level by 32% (p<0.05), vs VAT ...