{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T19:53:39Z","timestamp":1791575619999,"version":"4.3.4"},"reference-count":57,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"7","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2015,7,17]]},"abstract":"<jats:sec xml:lang=\"en\">\n            <jats:title>Background<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              Ubiquitous deletion of thioredoxin reductase 2 (\n              <jats:italic>Txnrd2<\/jats:italic>\n              ) in mice is embryonically lethal and associated with abnormal heart development, while constitutive, heart\u2010specific\n              <jats:italic>Txnrd2<\/jats:italic>\n              inactivation leads to dilated cardiomyopathy and perinatal death. The significance of\n              <jats:italic>Txnrd2<\/jats:italic>\n              in aging cardiomyocytes, however, has not yet been examined.\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              The tamoxifen\u2010inducible heart\u2010specific \u03b1\n              <jats:italic>MHC\u2010MerCreMer<\/jats:italic>\n              transgene was used to inactivate\n              <jats:italic>lox<\/jats:italic>\n              P\u2010flanked\n              <jats:italic>Txnrd2<\/jats:italic>\n              alleles in adult mice. Hearts and isolated mitochondria from aged knockout mice were morphologically and functionally analyzed. Echocardiography revealed a significant increase in left ventricular end\u2010systolic diameters in knockouts. Fractional shortening and ejection fraction were decreased compared with controls. Ultrastructural analysis of cardiomyocytes of aged mice showed mitochondrial degeneration and accumulation of autophagic bodies. A dysregulated autophagic activity was supported by higher levels of lysosome\u2010associated membrane protein 1 (LAMP1), microtubule\u2010associated protein 1A\/1B\u2010light chain 3\u2010I (\n              <jats:styled-content style=\"fixed-case\">LC<\/jats:styled-content>\n              3\u2010I), and\n              <jats:italic>p62<\/jats:italic>\n              in knockout hearts. Isolated\n              <jats:italic>Txnrd2<\/jats:italic>\n              \u2010deficient mitochondria used less oxygen and tended to produce more reactive oxygen species. Chronic hypoxia inducible factor 1, \u03b1 subunit stabilization and altered transcriptional and metabolic signatures indicated that energy metabolism is deregulated.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              These results imply a novel role of\n              <jats:italic>Txnrd2<\/jats:italic>\n              in sustaining heart function during aging and suggest that\n              <jats:italic>Txnrd2<\/jats:italic>\n              may be a modifier of heart failure.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/jaha.115.002153","type":"journal-article","created":{"date-parts":[[2015,7,22]],"date-time":"2015-07-22T01:40:33Z","timestamp":1437529233000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":60,"title":["Heart\u2010Specific Knockout of the Mitochondrial Thioredoxin Reductase (\n            <i>Txnrd2<\/i>\n            ) Induces Metabolic and Contractile Dysfunction in the Aging Myocardium"],"prefix":"10.1161","volume":"4","author":[{"given":"Claudia","family":"Kiermayer","sequence":"first","affiliation":[{"name":"Research Unit Comparative Medicine,  Helmholtz Zentrum M\u00fcnchen, German Research Center for Environmental Health, Neuherberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily","family":"Northrup","sequence":"additional","affiliation":[{"name":"Research Unit Comparative Medicine,  Helmholtz Zentrum M\u00fcnchen, German Research Center for Environmental Health, Neuherberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anja","family":"Schrewe","sequence":"additional","affiliation":[{"name":"Institute of Experimental Genetics,  Helmholtz Zentrum M\u00fcnchen, German Research Center for Environmental Health, Neuherberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Axel","family":"Walch","sequence":"additional","affiliation":[{"name":"Reserach Unit Analytical Pathology,  Helmholtz Zentrum M\u00fcnchen, German Research Center for Environmental Health, Neuherberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin Hrabe","family":"de Angelis","sequence":"additional","affiliation":[{"name":"Institute of Experimental Genetics,  Helmholtz Zentrum M\u00fcnchen, German Research Center for Environmental Health, Neuherberg, Germany"},{"name":"Chair of Experimental Genetics, Technische Universit\u00e4t M\u00fcnchen, Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank","family":"Schoensiegel","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine III, University of Heidelberg, Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans","family":"Zischka","sequence":"additional","affiliation":[{"name":"Institute of molecular Toxicology and Pharmacology,  Helmholtz Zentrum M\u00fcnchen, German Research Center for Environmental Health, Neuherberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cornelia","family":"Prehn","sequence":"additional","affiliation":[{"name":"Institute of Experimental Genetics, Genome Analysis Center, Helmholtz Zentrum M\u00fcnchen, German Research Center for Environmental Health, Neuherberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jerzy","family":"Adamski","sequence":"additional","affiliation":[{"name":"Institute of Experimental Genetics, Genome Analysis Center, Helmholtz Zentrum M\u00fcnchen, German Research Center for Environmental Health, Neuherberg, Germany"},{"name":"Chair of Experimental Genetics, Technische Universit\u00e4t M\u00fcnchen, Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raffi","family":"Bekeredjian","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine III, University of Heidelberg, Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Boris","family":"Ivandic","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine III, University of Heidelberg, Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Kupatt","sequence":"additional","affiliation":[{"name":"I. 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