Abstract 15487: Boosting Autophagy for the Reduction of Diabetes-Induced Endothelial Dysfunction

• Published in: Circulation (New York, N.Y.) N.Y.), 2022-11, Vol.146 (Suppl_1), p.A15487-A15487
• Main Authors: Forte, Maurizio, Schiavon, Sonia, Schirone, Leonardo, Vecchio, Daniele, D'Ambrosio, Luca, Frati, Giacomo, Sciarretta, Sebastiano
• Format: Article
• Language: English
• ISSN: 0009-7322; 1524-4539
• DOI: 10.1161/circ.146.suppl_1.15487

IntroductionDiabetes is one of the main cause of endothelial dysfunction. The molecular mechanisms underlying the effects of hyperglycaemia in endothelial cells still need to be clarified. Autophagy, a stress-responsive and self-renewal mechanism exerts beneficial effects in the cardiovascular system. However, its role in diabetes-induced endothelial dysfunction is unknown. HypothesisEndothelial autophagy is impaired in the presence of diabetes and restoration of autophagy may reduce diabetes-induced endothelial damage. MethodsThe effects of hyperglycaemia (HG, 30 mM for 6 and 24 hours) on autophagy, mitophagy and endothelial function were evaluated in vitro in human umbilical endothelial cells (HUVEC). Vascular reactivity experiments were performed in mesenteric arteries from wild-type mice (WT) treated with HG and in human saphenous veins from patients with peripheral artery diseases. Autophagy reactivation was carried out through ATG7 overexpression (ATG7ov) or through spermidine (SP) (100 nM), a natural activator of autophagy and inhibitor of p300. ResultsHG reduces autophagy (0.6 fold p