{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T01:55:06Z","timestamp":1787018106626,"version":"build-2736575974"},"reference-count":52,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"3","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2023,2,7]]},"abstract":"<jats:sec sec-type=\"background\" xml:lang=\"en\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p xml:lang=\"en\">Cardiomyopathy is a leading health threat in Duchenne muscular dystrophy (DMD). Cytosolic calcium upregulation is implicated in DMD cardiomyopathy. Calcium is primarily removed from the cytosol by the sarcoendoplasmic reticulum calcium ATPase (SERCA). SERCA activity is reduced in DMD. Improving SERCA function may treat DMD cardiomyopathy. Dwarf open reading frame (DWORF) is a recently discovered positive regulator for SERCA, hence, a potential therapeutic target.<\/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                      To study DWORF's involvement in DMD cardiomyopathy, we quantified DWORF expression in the heart of wild\u2010type mice and the mdx model of DMD. To test DWORF gene therapy, we engineered and characterized an adeno\u2010associated virus serotype 9\u2013DWORF vector. To determine if this vector can mitigate DMD cardiomyopathy, we delivered it to 6\u2010week\u2010old mdx mice (6\u00d710\n                      <jats:sup>12<\/jats:sup>\n                      vector genome particles\/mouse) via the tail vein. Exercise capacity, heart histology, and cardiac function were examined at 18\u2009months of age. We found DWORF expression was significantly reduced at the transcript and protein levels in mdx mice. Adeno\u2010associated virus serotype 9\u2013DWORF vector significantly enhanced SERCA activity. Systemic adeno\u2010associated virus serotype 9\u2010DWORF therapy reduced myocardial fibrosis and improved treadmill running, electrocardiography, and heart hemodynamics.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p xml:lang=\"en\">Our data suggest that DWORF deficiency contributes to SERCA dysfunction in mdx mice and that DWORF gene therapy holds promise to treat DMD cardiomyopathy.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/jaha.122.027480","type":"journal-article","created":{"date-parts":[[2023,1,25]],"date-time":"2023-01-25T05:54:44Z","timestamp":1674626084000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":29,"title":["Dwarf Open Reading Frame (DWORF) Gene Therapy Ameliorated Duchenne Muscular Dystrophy Cardiomyopathy in Aged mdx Mice"],"prefix":"10.1161","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7557-9585","authenticated-orcid":false,"given":"Emily D.","family":"Morales","sequence":"first","affiliation":[{"name":"Department of Molecular Microbiology and Immunology, School of Medicine The University of Missouri Columbia MO"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1640-2106","authenticated-orcid":false,"given":"Yongping","family":"Yue","sequence":"additional","affiliation":[{"name":"Department of Molecular Microbiology and Immunology, School of Medicine The University of Missouri Columbia MO"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thais B.","family":"Watkins","sequence":"additional","affiliation":[{"name":"Department of Molecular Microbiology and Immunology, School of Medicine The University of Missouri Columbia MO"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Molecular Microbiology and Immunology, School of Medicine The University of Missouri Columbia MO"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2594-5911","authenticated-orcid":false,"given":"Xiufang","family":"Pan","sequence":"additional","affiliation":[{"name":"Department of Molecular Microbiology and Immunology, School of Medicine The University of Missouri Columbia MO"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aaron M.","family":"Gibson","sequence":"additional","affiliation":[{"name":"Division of Molecular Cardiovascular Biology, Cincinnati Children\u2019s Hospital Medical Center The Heart Institute Cincinnati OH"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bryan","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Molecular Microbiology and Immunology, School of Medicine The University of Missouri Columbia MO"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8856-6791","authenticated-orcid":false,"given":"Omar","family":"Brito\u2010Estrada","sequence":"additional","affiliation":[{"name":"Division of Molecular Cardiovascular Biology, Cincinnati Children\u2019s Hospital Medical Center The Heart Institute Cincinnati OH"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gang","family":"Yao","sequence":"additional","affiliation":[{"name":"Department of Biomedical, Biological &amp; 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