srt2104 and Diabetic-Angiopathies

Endothelial dysfunction contributes to diabetic macrovascular complications. Sirtuin 1 (SIRT1) protects against diabetic vasculopathy. SRT2104 is a novel SIRT1 activator and was not previously studied for its effects on diabetes-induced aortic endothelial dysfunction. Additionally, whether or to what extent deacetylation of P53, a substrate of SIRT1, is required for the effects of SIRT1 activation was unclear, given the fact that SIRT1 has multiple targets. Moreover, little was known about the pathogenic role of P53 in diabetes-induced aortic injury. To these ends, diabetes was induced by streptozotocin in C57BL/6 mice. The diabetic mice developed enhanced aortic contractility, oxidative stress, inflammation, P53 hyperacetylation and a remarkable decrease in SIRT1 protein, the effects of which were rescued by SRT2104. In HG-treated endothelial cells (ECs),

Topics: Animals; Aorta; Cells, Cultured; Diabetes Mellitus, Experimental; Diabetic Angiopathies; Down-Regulation; Endothelium, Vascular; Heterocyclic Compounds, 2-Ring; Male; Mice; Mice, Inbred C57BL; Signal Transduction; Tumor Suppressor Protein p53