SIRT1 and Hyperglycemia: Specifically, hyperglycemia and hyperlipidemia reduced Sirt1 activation of theTIMP3 promoter, which caused increased endothelial activation and inflammation withinatherosclerotic plaques in diabetic subjects.51Because soluble adhesion molecules such as VCAM‐1 and ICAM‐1 are shed by ADAM17, it isintriguing to hypothesize that a Sirt1‐TIMP3‐ADAM17 pathway is active early in thepathogenesis of endothelial dysfunction.