{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T19:12:37Z","timestamp":1792696357103,"version":"4.5.0"},"reference-count":292,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2023,10,6]],"date-time":"2023-10-06T00:00:00Z","timestamp":1696550400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Michigan Medicine-PKUHSC Joint Institute for Translational and Clinical Research Discovery","award":["G023112"],"award-info":[{"award-number":["G023112"]}]},{"name":"Michigan Medicine-PKUHSC Joint Institute for Translational and Clinical Research Discovery","award":["R01 HL149363"],"award-info":[{"award-number":["R01 HL149363"]}]},{"name":"University of Michigan Frankel Cardiovascular Center 2022 Inaugural award","award":["G023112"],"award-info":[{"award-number":["G023112"]}]},{"name":"University of Michigan Frankel Cardiovascular Center 2022 Inaugural award","award":["R01 HL149363"],"award-info":[{"award-number":["R01 HL149363"]}]},{"name":"University of Michigan Frankel Cardiovascular Center C. Steve Baum Stem Cell Research Award","award":["G023112"],"award-info":[{"award-number":["G023112"]}]},{"name":"University of Michigan Frankel Cardiovascular Center C. Steve Baum Stem Cell Research Award","award":["R01 HL149363"],"award-info":[{"award-number":["R01 HL149363"]}]},{"name":"NIH","award":["G023112"],"award-info":[{"award-number":["G023112"]}]},{"name":"NIH","award":["R01 HL149363"],"award-info":[{"award-number":["R01 HL149363"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>Atrial fibrillation (AF) is the most common type of cardiac arrhythmia and its prevalence increases with age. The irregular and rapid contraction of the atria can lead to ineffective blood pumping, local blood stasis, blood clots, ischemic stroke, and heart failure. NADPH oxidases (NOX) and mitochondria are the main sources of reactive oxygen species in the heart, and dysregulated activation of NOX and mitochondrial dysfunction are associated with AF pathogenesis. NOX- and mitochondria-derived oxidative stress contribute to the onset of paroxysmal AF by inducing electrophysiological changes in atrial myocytes and structural remodeling in the atria. Because high atrial activity causes cardiac myocytes to expend extremely high energy to maintain excitation-contraction coupling during persistent AF, mitochondria, the primary energy source, undergo metabolic stress, affecting their morphology, Ca2+ handling, and ATP generation. In this review, we discuss the role of oxidative stress in activating AF-triggered activities, regulating intracellular Ca2+ handling, and functional and anatomical reentry mechanisms, all of which are associated with AF initiation, perpetuation, and progression. Changes in the extracellular matrix, inflammation, ion channel expression and function, myofibril structure, and mitochondrial function occur during the early transitional stages of AF, opening a window of opportunity to target NOX and mitochondria-derived oxidative stress using isoform-specific NOX inhibitors and mitochondrial ROS scavengers, as well as drugs that improve mitochondrial dynamics and metabolism to treat persistent AF and its transition to permanent AF.<\/jats:p>","DOI":"10.3390\/antiox12101833","type":"journal-article","created":{"date-parts":[[2023,10,6]],"date-time":"2023-10-06T07:49:29Z","timestamp":1696578569000},"page":"1833","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":62,"title":["NADPH Oxidases and Oxidative Stress in the Pathogenesis of Atrial Fibrillation"],"prefix":"10.3390","volume":"12","author":[{"given":"Roberto","family":"Ramos-Mondrag\u00f3n","sequence":"first","affiliation":[{"name":"Department of Pharmacology, University of Michigan, 1150 West Medical Center Drive, 2301 Medical Science Research Building III, Ann Arbor, MI 48109, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1604-1603","authenticated-orcid":false,"given":"Andrey","family":"Lozhkin","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Frankel Cardiovascular Center, University of Michigan, Ann Arbor, MI 48019, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aleksandr E.","family":"Vendrov","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Frankel Cardiovascular Center, University of Michigan, Ann Arbor, MI 48019, USA"}],"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, MI 48019, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lori L.","family":"Isom","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, University of Michigan, 1150 West Medical Center Drive, 2301 Medical Science Research Building III, Ann Arbor, MI 48109, USA"},{"name":"Department of Neurology, University of Michigan, Ann Arbor, MI 48109, USA"},{"name":"Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI 48109, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0590-0908","authenticated-orcid":false,"given":"Nageswara R.","family":"Madamanchi","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Frankel Cardiovascular Center, University of Michigan, Ann Arbor, MI 48019, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,10,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"946","DOI":"10.1161\/01.CIR.98.10.946","article-title":"Impact of atrial fibrillation on the risk of death: The Framingham Heart Study","volume":"98","author":"Benjamin","year":"1998","journal-title":"Circulation"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1373\/clinchem.2016.255182","article-title":"Application of biomarkers for risk stratification in patients with atrial fibrillation","volume":"63","author":"Hijazi","year":"2017","journal-title":"Clin. 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