SRT2104 attenuates diabetes-induced aortic endothelial dysfunction via inhibition of P53

摘要: Endothelial dysfunction contributes to diabetic macrovascular complications. Sirtuin 1 (SIRT1) protects against vasculopathy. SRT2104 is a novel SIRT1 activator and was not previously studied for its effects on diabetes-induced aortic endothelial dysfunction. Additionally, whether or what extent deacetylation of P53, substrate SIRT1, required the activation unclear, given fact that has multiple targets. Moreover, little known about pathogenic role P53 in injury. To these ends, diabetes induced by streptozotocin C57BL/6 mice. The mice developed enhanced contractility, oxidative stress, inflammation, hyperacetylation remarkable decrease protein, which were rescued SRT2104. In HG-treated cells (ECs), siRNA produced similar induction inhibition acetylation, stress inflammation. Interestingly, failed further enhance presence siRNA. nutlin3a completely abolished SRT2104's protection HG-induced Further, forced increased contractility healthy generated inflammation both normal glucose-cultured ECs aortas Collectively, present study demonstrates predominantly mediates highlights