Protective role of adiponectin on endothelial dysfunction induced by AGEs: A clinical and experimental approach

ObjectiveObesity is characterized by low levels of adiponectin, an adipocytes derived hormone, and by an inflammatory component. Endothelial dysfunction is often found in overweight/obesity, diabetes, and atherosclerosis. Advanced glycation end products (AGEs) induce endothelial dysfunction and are linked to diabetes and increased atherogenicity and inflammation. The aim of the study was to investigate the possible link between adiponectin and N(epsilon)-(carboxymethyl) lysine (CML), the predominant adduct of circulating AGEs in overweight patients, and, in an in vitro model, to test the hypothesis that adiponectin acts as modulator of endothelial dysfunction, induced by AGEs.ResultsIn 108 overweight patients, plasma levels of CML correlated inversely with adiponectin levels. Pre-incubation of human vein endothelial cells (HUVECs) with physiological concentrations of adiponectin, followed by stimulation with AGEs, reduced vascular adhesion molecule-1 (VCAM-1) and E-selectin expression, as assessed by surface enzyme immunoassay.ConclusionsTaken together, these findings demonstrate an inverse correlation between CML and adiponectin levels in overweight patients and a protective role of adiponectin on endothelial dysfunction induced by AGEs, suggesting its key role in the treatment of the vascular complications of obesity/metabolic syndrome.

Graphical AbstractEndothelial dysfunction is a common denominator between metabolic and cardiovascular disease. Adiponectin correlates inversely with AGE levels in overweight patients and counteracts VCAM-1 and E-selectin endothelial expression induced by AGEs.Figure optionsDownload as PowerPoint slideResearch Highlights
► Adiponectin and CML levels inversely correlate in overweight subjects.
► Adiponectin inhibit endothelial adhesion molecule expression induced by AGEs.
► Adiponectin can have a key role in the treatment of the vascular complications in overweight/obesity.