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

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/142527/1/jah32679-sup-0001-SupInfo.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/142527/2/jah32679_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/142527/3/jah32679.pd

Mitochondrial Oxidative Stress in Aortic Stiffening With Age: The Role of Smooth Muscle Cell Function

Age-related aortic stiffness is an independent risk factor for cardiovascular diseases. Although oxidative stress is implicated in aortic stiffness, the underlying molecular mechanisms remain unelucidated. Here, we examined the source of oxidative stress in aging and its effect on smooth muscle cell (SMC) function and aortic compliance using mutant mouse models

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

Background: Atherosclerosis 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 Results: Compared with Apoe−/−, middle‐aged Apoe−/−/Sod2+/− mice had increased vascular wall reactive oxygen species (P Conclusions: Enhanced mitochondrial oxidative stress under hyperlipidemic conditions in aging induces plaque instability, in part by increasing smooth muscle cell apoptosis, necrotic core expansion, and matrix degradation. Targeting mitochondrial reactive oxygen species or its effectors may be a viable therapeutic strategy to prevent aging‐associated and oxidative stress–related atherosclerosis complications