In our previous studies in ApoE/LDLR−/− mice, it was not possible to dissect the effects of hypercholesterolaemia, atherosclerosis and ageing on the progression of endothelial dysfunction, since complex and multifactorial endothelial dysfunction was detected already at the age of 8 weeks, while atherosclerotic plaques were already present at the age range of 12–14 weeks in ApoE/LDLR−/− mice [30]. Here, APOE is linked to Hypercholesterolemia.