We claim that robust compensatory mechanisms in coronary circulation, including increased vascular responsiveness to NO (Fig. 3) and increased generation of PGI2 (Fig. 4B,C) that are triggered in the early phase of atherosclerosis development, could, at least partly, account for preserved V’O2max and running exercise capacity of female ApoE/LDLR−/− mice as well as their full cardiac adaptation to exercise occurring even at the stage of advanced atherosclerosis at the age of 6–8 months. This evidence concerns the gene LDLR and atherosclerosis.