{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T09:52:01Z","timestamp":1786960321513,"version":"build-2736575974"},"reference-count":62,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"11","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2017,11]]},"abstract":"<jats:sec xml:lang=\"en\">\n            <jats:title>Background<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              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\u2010type mice and that young\n              <jats:italic>Apoe<\/jats:italic>\n              <jats:sup>\u2212\/\u2212<\/jats:sup>\n              \/\n              <jats:italic>Sod2<\/jats:italic>\n              <jats:sup>+\/\u2212<\/jats:sup>\n              had increased mitochondrial\n              <jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content>\n              damage and atherosclerosis versus young\n              <jats:italic>Apoe<\/jats:italic>\n              <jats:sup>\u2212\/\u2212<\/jats:sup>\n              mice. Here we investigated the effects of superoxide dismutase 2 deficiency on atherosclerosis progression and plaque morphology in middle\u2010aged\n              <jats:italic>Apoe<\/jats:italic>\n              <jats:sup>\u2212\/\u2212<\/jats:sup>\n              mice.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Methods and Results<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              Compared with\n              <jats:italic>Apoe<\/jats:italic>\n              <jats:sup>\u2212\/\u2212<\/jats:sup>\n              , middle\u2010aged\n              <jats:italic>Apoe<\/jats:italic>\n              <jats:sup>\u2212\/\u2212<\/jats:sup>\n              \/\n              <jats:italic>Sod2<\/jats:italic>\n              <jats:sup>+\/\u2212<\/jats:sup>\n              mice had increased vascular wall reactive oxygen species (\n              <jats:italic>P<\/jats:italic>\n              &lt;0.05) and higher atherosclerotic lesion area (\n              <jats:italic>P<\/jats:italic>\n              &lt;0.001). The atherosclerotic plaques in middle\u2010aged\n              <jats:italic>Apoe<\/jats:italic>\n              <jats:sup>\u2212\/\u2212<\/jats:sup>\n              \/\n              <jats:italic>Sod2<\/jats:italic>\n              <jats:sup>+\/\u2212<\/jats:sup>\n              mice had an increased necrotic core with higher inflammatory cell infiltration, a thinned fibrous cap with depleted smooth muscle content, and intraplaque hemorrhage. In addition, the plaque shoulder area had higher levels of calpain\u20102, caspase\u20103, and matrix metalloproteinase\u20102 in intimal smooth muscle cells and depleted fibrous cap collagen. Targeting mitochondrial reactive oxygen species with Mito\n              <jats:styled-content style=\"fixed-case\">TEMPO<\/jats:styled-content>\n              attenuated features of atherosclerotic plaque vulnerability in middle\u2010aged\n              <jats:italic>Apoe<\/jats:italic>\n              <jats:sup>\u2212\/\u2212<\/jats:sup>\n              \/\n              <jats:italic>Sod2<\/jats:italic>\n              <jats:sup>+\/\u2212<\/jats:sup>\n              mice by lowering expression of calpain\u20102, caspase\u20103, and matrix metalloproteinase\u20102 and decreasing smooth muscle cell apoptosis and matrix degradation.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p xml:lang=\"en\">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\u2010associated and oxidative stress\u2013related atherosclerosis complications.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/jaha.117.006775","type":"journal-article","created":{"date-parts":[[2017,10,28]],"date-time":"2017-10-28T00:10:32Z","timestamp":1509149432000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":61,"title":["Attenuated Superoxide Dismutase 2 Activity Induces Atherosclerotic Plaque Instability During Aging in Hyperlipidemic Mice"],"prefix":"10.1161","volume":"6","author":[{"given":"Aleksandr E.","family":"Vendrov","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, Frankel Cardiovascular Center, University of Michigan, Ann Arbor, MI"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark D.","family":"Stevenson","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Frankel Cardiovascular Center, University of Michigan, Ann Arbor, MI"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samthosh","family":"Alahari","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Frankel Cardiovascular Center, University of Michigan, Ann Arbor, MI"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hua","family":"Pan","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Sciences, USF Health Heart Institute, Morsani College of Medicine, University of South Florida, Tampa, FL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuel A.","family":"Wickline","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Sciences, USF Health Heart Institute, Morsani College of Medicine, University of South Florida, Tampa, FL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nageswara R.","family":"Madamanchi","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Frankel Cardiovascular Center, University of Michigan, Ann Arbor, MI"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marschall S.","family":"Runge","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Frankel Cardiovascular Center, University of Michigan, Ann Arbor, 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