SIRT1 and Hypercholesterolemia: For example, previous studies have demonstrated that upregulation of Sirt1 improves aortic endothelial function in the setting of both hypercholesterolemia (Zhang et al., 2008) and high fat feeding (Fry et al., 2016) and Sirt1 has been reported to directly modulate endothelial function in small and large arteries through deacetylation and subsequent activation of eNOS, helping to maintain vascular homeostasis (Mattagajasingh et al., 2007).