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We evaluated whether high inorganic phosphate (Pi) intake causes atrial remodeling and increased atrial fibrillation (AF) risk.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The 5\/6 nephrectomized chronic kidney disease (CKD) mice were fed a high\u2010Pi (2%) diet for 10\u2009weeks. AF vulnerability was evaluated through transesophageal burst atrial pacing. Phosphoproteomic, Western blotting, and immunohistochemistry were used to evaluate the effects of high Pi in atrial fibroblasts, atrial myocytes, and HL\u20101 myocytes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>CKD and sham mice fed a high\u2010Pi diet exhibited increased AF vulnerability, atrial fibrosis, and oxidative stress compared with mice fed a normal diet. Compared with normal (1\u2009mM) Pi, high (2\u2009mM) Pi significantly increased the activity of atrial fibroblasts and mitochondrial oxidative stress. Phosphoproteomic analysis revealed that compared with normal Pi, high Pi considerably increased the phosphorylation of intracellular proteins in atrial fibroblasts, including proteins related to NF\u2010\u03baB signaling and STAT3. Inhibition of NF\u2010\u03baB, STAT3, and Nox4 by small interfering RNA reduced the high\u2010Pi\u2010induced expression of collagen. In HL\u20101 myocytes, the high Pi induced the degradation of myofibril proteins and hyperphosphorylation of RyR2, which was abolished by Nox4 and CaMKII inhibition. Switching back to a normal\u2010Pi diet improved the atrial abnormalities induced by high\u2010Pi diet.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>High\u2010Pi intake causes atrial structural and electrical remodeling and increases AF vulnerability, which is mediated through STAT3\/NF\u2010\u03baB signaling and oxidative stress. High dietary Pi intake can exert detrimental effects on atria and may increase AF risk.<\/jats:p><\/jats:sec>","DOI":"10.1111\/apha.13964","type":"journal-article","created":{"date-parts":[[2023,3,17]],"date-time":"2023-03-17T13:09:55Z","timestamp":1679058595000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["High\u2010phosphate diet causes atrial remodeling and increases atrial fibrillation vulnerability via <scp>STAT3\/NF\u2010\u03baB<\/scp> signaling and oxidative stress"],"prefix":"10.1111","volume":"238","author":[{"given":"Yu\u2010Juei","family":"Hsu","sequence":"first","affiliation":[{"name":"Division of Nephrology, Department of Internal Medicine Tri\u2010Service General Hospital  Taipei Taiwan"},{"name":"Department of Biochemistry National Defense Medical Center  Taipei 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