In SIRT6 knockout mice, atherosclerotic plaque was enlarged, plaque vulnerability was enhanced, and the expression of ICAM-1 in aortic endothelial cells was significantly up-regulated, implying that SIRT6 is the primary negative regulator of endothelial dysfunction and atherosclerotic development (Liu et al., 2016). This evidence concerns the gene SIRT6 and endothelial dysfunction.