Attenuated Superoxide Dismutase 2 Activity Induces Atherosclerotic Plaque Instability During Aging in Hyperlipidemic Mice

BackgroundAtherosclerosis progression during aging culminates in the development of vulnerable plaques, which may increase the risk of cardiovascular events. Increased generation and/or decreased scavenging of reactive oxygen species in the vascular wall are major contributors to atherogenesis. We previously showed that superoxide dismutase 2 deficiency increased vascular oxidative stress and reduced aortic compliance in aged wild‐type mice and that young Apoe−/−/Sod2+/− had increased mitochondrial DNA damage and atherosclerosis versus young Apoe−/− mice. Here we investigated the effects of superoxide dismutase 2 deficiency on atherosclerosis progression and plaque morphology in middle‐aged Apoe−/− mice. Methods and ResultsCompared with Apoe−/−, middle‐aged Apoe−/−/Sod2+/− mice had increased vascular wall reactive oxygen species (P