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Pepper Center","award":["P30AG028747"],"award-info":[{"award-number":["P30AG028747"]}]},{"DOI":"10.13039\/100000050","name":"NHLBI","doi-asserted-by":"crossref","award":["R01 HL142290"],"award-info":[{"award-number":["R01 HL142290"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,12,8]]},"abstract":"<jats:p>\n                    Mechanistically driven therapies for atrial fibrillation (AF), the most common cardiac arrhythmia, are urgently needed, the development of which requires improved understanding of the cellular signaling pathways that facilitate the structural and electrophysiological remodeling that occurs in the atria. Similar to humans, increased persistent Na\n                    <jats:sup>+<\/jats:sup>\n                    current leads to the development of an atrial myopathy and spontaneous and long-lasting episodes of AF in mice. How increased persistent Na\n                    <jats:sup>+<\/jats:sup>\n                    current causes both structural and electrophysiological remodeling in the atria is unknown. We crossbred mice expressing human F1759A-Na\n                    <jats:sub>V<\/jats:sub>\n                    1.5 channels with mice expressing human mitochondrial catalase (mCAT). Increased expression of mCAT attenuated mitochondrial and cellular reactive oxygen species (ROS) and the structural remodeling that was induced by persistent F1759A-Na\n                    <jats:sup>+<\/jats:sup>\n                    current. Despite the heterogeneously prolonged atrial action potential, which was unaffected by the reduction in ROS, the incidences of spontaneous AF, pacing-induced after-depolarizations, and AF were substantially reduced. Expression of mCAT markedly reduced persistent Na\n                    <jats:sup>+<\/jats:sup>\n                    current\u2013induced ryanodine receptor oxidation and dysfunction. In summary, increased persistent Na\n                    <jats:sup>+<\/jats:sup>\n                    current in atrial cardiomyocytes, which is observed in patients with AF, induced atrial enlargement, fibrosis, mitochondrial dysmorphology, early after-depolarizations, and AF, all of which can be attenuated by resolving mitochondrial oxidative stress.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.147371","type":"journal-article","created":{"date-parts":[[2021,10,28]],"date-time":"2021-10-28T12:00:41Z","timestamp":1635422441000},"source":"Crossref","is-referenced-by-count":32,"title":["Attenuating persistent sodium current\u2013induced atrial myopathy and fibrillation by preventing mitochondrial oxidative stress"],"prefix":"10.1172","volume":"6","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4786-3722","authenticated-orcid":true,"given":"Uma Mahesh R.","family":"Avula","sequence":"first","affiliation":[{"name":"Division of Cardiology, Department of Medicine, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9533-7367","authenticated-orcid":true,"given":"Haikel","family":"Dridi","sequence":"additional","affiliation":[{"name":"Department of Physiology and Cellular Biophysics and Clyde & Helen Wu Center for Molecular Cardiology, Vagelos College of Physicians and Surgeons, Columbia University, New York, New York, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bi-xing","family":"Chen","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Medicine, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi","family":"Yuan","sequence":"additional","affiliation":[{"name":"Department of Physiology and Cellular Biophysics and Clyde & Helen Wu Center for Molecular Cardiology, Vagelos College of Physicians and Surgeons, Columbia University, New York, New York, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander N.","family":"Katchman","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Medicine, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5807-3574","authenticated-orcid":true,"given":"Steven R.","family":"Reiken","sequence":"additional","affiliation":[{"name":"Department of Physiology and Cellular Biophysics and Clyde & Helen Wu Center for Molecular Cardiology, Vagelos College of Physicians and Surgeons, Columbia University, New York, New York, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6873-3217","authenticated-orcid":true,"given":"Amar D.","family":"Desai","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Medicine, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0065-8825","authenticated-orcid":true,"given":"Samantha","family":"Parsons","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Medicine, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8110-5036","authenticated-orcid":true,"given":"Haajra","family":"Baksh","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Medicine, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elaine","family":"Ma","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Medicine, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1408-7541","authenticated-orcid":true,"given":"Parmanand","family":"Dasrat","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Medicine, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruiping","family":"Ji","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Medicine, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yejun","family":"Lin","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Medicine, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine","family":"Sison","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Medicine, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8488-2180","authenticated-orcid":true,"given":"W. 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