Abstract P342: Sirt 1 on Endothelial Dysfunction in Small Arteries From Obese Patients

Abstract

Obesity is associated with endothelial dysfunction, characterised by a reduced nitric oxide (NO) bioavailability due to increased reactive oxygen species (ROS). Sirtuins, and more specifically Sirt-1, are enzymatic proteins involved in regulation of glucose metabolism, inflammation and intracellular levels of ROS. This study aimed to determine the role of Sirt-1 in regulating NO bioavailability of small resistance arteries isolated from subcutaneous tissue of obese patients. 10 subjects (5 with severe obesity, Ob; 5 normal weight controls, Ctrl) underwent biopsy of subcutaneous adipose tissue during laparoscopic bariatric surgery. Function of small arteries was assessed with pressure micromyography. Endothelial-dependent vasodilation (VDep) and NO production was assessed by acetylcholine (ACh, 0,001-100μM), with and without pre-incubation with L-NAME (100μM). The influence of sirtuins on NO bioavailability was assessed repeating Ach with a selective Sirt-1 agonist (SRT-1720, 1μM), alone or plus L-NAME. Ob showed a reduced response to Ach vs Ctrl (P<0.001), associated with a reduced inhibition of L-NAME on Ach (Ob: P=0.002; Ctrl: P<0.001). SRT-1720 improved the VDed induced by Ach (P<0.001) in Ob, although it did not reach values from Ctrl. The simultaneous incubation with L-NAME and SRT-1720 before Ach stimulation abolished the VDed obtained with the incubation of SRT-1720 in the Ob group (SRT-1720 vs SRT-1720+L-NAME: P<0.001). In small arteries of Ob, stimulation of Sirt-1 activity partially restores endothelial function due to an improved NO bioavailability.