APOE and atherosclerosis: Indeed, mtDNA damage is present in the aortas, hearts, and circulating leukocytes of patients with atherosclerosis7–9 and is an early event in atherogenesis in apolipoprotein E–deficient (ApoE−/−) mice.8 Furthermore, large-scale induction of mtDNA damage can directly promote atherosclerosis and plaque vulnerability in ApoE−/− mice independent of ROS.9 However, it is not clear what causes mtDNA damage in atherosclerosis and importantly whether the endogenous levels of mtDNA damage seen in mouse or human atherosclerosis are sufficient to cause mitochondrial dysfunction.