{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T02:55:11Z","timestamp":1790823311722,"version":"4.1.0"},"reference-count":79,"publisher":"SAGE Publications","issue":"1","license":[{"start":{"date-parts":[[2019,5,21]],"date-time":"2019-05-21T00:00:00Z","timestamp":1558396800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Antioxidants &amp; Redox Signaling"],"published-print":{"date-parts":[[2019,7]]},"abstract":"<jats:sec>\n                    <jats:title>Aims:<\/jats:title>\n                    <jats:p>Oxidative stress is implicated in cardiomyocyte cell death and cardiac remodeling in the failing heart. The role of NADPH oxidase 4 (NOX4) in cardiac adaptation to pressure overload is controversial, but its function in myocardial ischemic stress has not been thoroughly elucidated. This study examined the function of NOX4 in the pathogenesis of ischemic heart failure, utilizing mouse models, cell culture, and human heart samples.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      <jats:italic toggle=\"yes\">\n                        Nox4\n                        <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      <\/jats:italic>\n                      mice showed a protective phenotype in response to permanent left anterior descending coronary artery ligation with smaller infarction area, lower cardiomyocyte cross-sectional area, higher capillary density, and less cell death\n                      <jats:italic toggle=\"yes\">versus<\/jats:italic>\n                      wild-type (WT) mice.\n                      <jats:italic toggle=\"yes\">\n                        Nox4\n                        <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      <\/jats:italic>\n                      mice had lower activity of soluble epoxide hydrolase (sEH), a potent regulator of inflammation.\n                      <jats:italic toggle=\"yes\">\n                        Nox4\n                        <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      <\/jats:italic>\n                      mice also showed a 50% reduction in the number of infiltrating CD68\n                      <jats:sup>+<\/jats:sup>\n                      macrophages in the peri-infarct zone\n                      <jats:italic toggle=\"yes\">versus<\/jats:italic>\n                      WT mice. Adenoviral overexpression of\n                      <jats:italic toggle=\"yes\">NOX4<\/jats:italic>\n                      in cardiomyoblast cells increased sEH expression and activity and CCL4 and CCL5 levels; inhibition of sEH activity in\n                      <jats:italic toggle=\"yes\">NOX4<\/jats:italic>\n                      overexpressing cells attenuated the cytokine levels. Human hearts with ischemic cardiomyopathy showed adverse cardiac remodeling, increased NOX4 and sEH protein expression and CCL4 and CCL5 levels compared with control nonfailing hearts.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Innovation and Conclusion:<\/jats:title>\n                    <jats:p>\n                      These data from the\n                      <jats:italic toggle=\"yes\">\n                        Nox4\n                        <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      <\/jats:italic>\n                      mouse model and human heart tissues show for the first time that oxidative stress from increased NOX4 expression has a functional role in ischemic heart failure. One mechanism by which NOX4 contributes to ischemic heart failure is by increasing inflammatory cytokine production\n                      <jats:italic toggle=\"yes\">via<\/jats:italic>\n                      enhanced sEH activity.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1089\/ars.2018.7548","type":"journal-article","created":{"date-parts":[[2018,11,19]],"date-time":"2018-11-19T02:16:42Z","timestamp":1542593802000},"page":"39-58","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":44,"title":["NADPH Oxidase 4 Regulates Inflammation in Ischemic Heart Failure: Role of Soluble Epoxide Hydrolase"],"prefix":"10.1177","volume":"31","author":[{"given":"Mark D.","family":"Stevenson","sequence":"first","affiliation":[{"name":"Frankel Cardiovascular Center, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chandrika","family":"Canugovi","sequence":"additional","affiliation":[{"name":"Frankel Cardiovascular Center, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aleksandr E.","family":"Vendrov","sequence":"additional","affiliation":[{"name":"Frankel Cardiovascular Center, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takayuki","family":"Hayami","sequence":"additional","affiliation":[{"name":"Frankel Cardiovascular Center, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dawn E.","family":"Bowles","sequence":"additional","affiliation":[{"name":"Department of Surgery, Duke University School of Medicine, Durham, North 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