P2624
The contribution of Sirtuin-1 to the obesity-related endothelial dysfunction

Extract

Background: Obesity represents a major risk factor for cardiovascular disease, promoting vascular remodelling and accelerating early vascular ageing. Endothelial dysfunction due to a reduced nitric oxide (NO) availability contributes to vascular remodelling in obesity. Sirtuin-1 (Sirt-1) is a protein with anti-oxidant capacities, downregulated with ageing and promoting endothelial-dependent vascular relaxation by activating endothelial nitric oxide synthetase (eNOS) in culture and animal experiments. However, the impact of Sirt-1 on endothelial function in humans remains unknown.

Purpose: To assess the influence of Sirt-1 on endothelial function of patients with severe obesity and its potential effects on endothelial NO availability.

Methods: Small resistance arteries were isolated from subcutaneous tissue of 23 patients with severe obesity (Ob) undergoing bariatric surgery and 40 normal weight controls (Nw) undergoing inguinal hernia repair or elective cholecystectomy. Pressurised miocromyography was used to assess media-to-lumen ratio (M/L), media cross-sectional area (MCSA) and endothelial-dependent vasodilation (VD) by means of dose-response curves to Acetylcholine (Ach). To explore the influence of Sirt-1 on endothelial function, Ach was repeated after pre-incubation with SRT1720, a Sirt-1 agonist. Pre-incubation with L-NAME (inhibitor of eNOS) was used to define the proportion of Ach-induced VD dependent from NO availability.