SIRT6 and Hypercholesterolemia: Moreover, the data obtained in hypercholesterolemic (LA, LDLR−/−APOB100/100) mice that were WT (LA-SIRT6+/+) or heterozygous for SIRT6 (LA-SIRT6+/−) suggested the context-dependent role of SIRT6 in hypercholesterolemia-induced valvular dysfunction, and modulation of hypertrophic responses to progressive increases in LV afterload [74–76].