{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T18:51:06Z","timestamp":1790016666572,"version":"4.0.1"},"reference-count":55,"publisher":"American Society for Clinical Investigation","issue":"22","license":[{"start":{"date-parts":[[2025,11,24]],"date-time":"2025-11-24T00:00:00Z","timestamp":1763942400000},"content-version":"vor","delay-in-days":48,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000098","name":"NIH Clinical Center","doi-asserted-by":"crossref","award":["NHLBI R03HL146881"],"award-info":[{"award-number":["NHLBI R03HL146881"]}],"id":[{"id":"10.13039\/100000098","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000098","name":"NIH Clinical Center","doi-asserted-by":"crossref","award":["NHLBI R01 HL152236"],"award-info":[{"award-number":["NHLBI R01 HL152236"]}],"id":[{"id":"10.13039\/100000098","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,11,24]]},"abstract":"<jats:p>Atrial fibrillation (AF) is a prevalent arrhythmia with known detriments such as heart failure, stroke, and cognitive decline even in patients without prior stroke. The mechanisms by which AF leads to cognitive dysfunction are yet unknown, and there is a lack of animal models to study this disease process. We previously developed a murine model of spontaneous and prolonged episodes of AF, a double transgenic mouse model with cardiac-specific expression of a gain-of-function mutant voltage-gated sodium channel (DTG-AF mice). Herein, we show, for the first time to our knowledge, a murine model of AF without any cerebral infarcts exhibiting cognitive dysfunction, including impaired visual learning and cognitive flexibility on touch screen testing. Mesenteric resistance arterial function of DTG-AF mice showed significant loss of myogenic tone, increased wall thickness and distensibility, and mitochondrial dysfunction. Brain pial arteries also showed increased wall thickness and mitochondrial enlargement. Furthermore, DTG-AF mice have decreased brain perfusion on laser speckle contrast imaging compared with controls. Cumulatively, these findings demonstrate that AF leads to vascular structural and functional alterations necessary for dynamic cerebral autoregulation, resulting in increased cerebral stress and cognitive dysfunction. Expression of mitochondrial catalase (mCAT) to reduce mitochondrial reactive oxygen species (ROS) was sufficient to prevent vascular dysfunction due to AF, restore perfusion, and improve cognitive flexibility.<\/jats:p>","DOI":"10.1172\/jci.insight.189850","type":"journal-article","created":{"date-parts":[[2025,10,7]],"date-time":"2025-10-07T16:00:26Z","timestamp":1759852826000},"source":"Crossref","is-referenced-by-count":5,"title":["Atrial fibrillation\u2013induced neurocognitive and vascular dysfunction is averted by mitochondrial oxidative stress reduction"],"prefix":"10.1172","volume":"10","author":[{"given":"Pavithran","family":"Guttipatti","sequence":"first","affiliation":[{"name":"Division of Cardiology, Department of Medicine, Vagelos College of Physicians and Surgeons, Columbia University, New York, New York, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruiping","family":"Ji","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Medicine, Vagelos College of Physicians and Surgeons, Columbia University, New York, New York, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Najla","family":"Saadallah","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Medicine, Vagelos College of Physicians and Surgeons, Columbia University, New York, New York, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4786-3722","authenticated-orcid":true,"given":"Uma Mahesh R.","family":"Avula","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Medicine, Vagelos College of Physicians and Surgeons, Columbia University, New York, New York, USA."},{"name":"Department of Medicine, University of Mississippi, Jackson, Mississippi, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deniz Z.","family":"Sonmez","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Medicine, Vagelos College of Physicians and Surgeons, Columbia University, New York, New York, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Albert","family":"Fang","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Medicine, Vagelos College of Physicians and Surgeons, Columbia University, New York, New York, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Li","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Medicine, 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, Vagelos College of Physicians and Surgeons, Columbia University, New York, New York, USA."}],"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, Vagelos College of Physicians and Surgeons, Columbia University, New York, New York, USA."}],"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, Vagelos College of Physicians and Surgeons, Columbia University, New York, New York, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine","family":"Sison","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Medicine, Vagelos College of Physicians and Surgeons, Columbia University, New York, New York, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanping","family":"Sun","sequence":"additional","affiliation":[{"name":"Oncology Precision Therapeutics and Imaging Core, Herbert Irving Comprehensive Cancer Center, Columbia University, New York, New York, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chris N.","family":"Goulbourne","sequence":"additional","affiliation":[{"name":"Center for Dementia Research, Nathan S. 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