{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T05:44:03Z","timestamp":1793339043373,"version":"4.5.0"},"reference-count":74,"publisher":"American Society for Clinical Investigation","issue":"3","license":[{"start":{"date-parts":[[2022,2,11]],"date-time":"2022-02-11T00:00:00Z","timestamp":1644537600000},"content-version":"vor","delay-in-days":3,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["81873486"],"award-info":[{"award-number":["81873486"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["81770327"],"award-info":[{"award-number":["81770327"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Natural Scientific Fund of Jiangsu province","award":["BK20161226"],"award-info":[{"award-number":["BK20161226"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,2,8]]},"abstract":"<jats:p>\n                    There is a high prevalence of ventricular arrhythmias related to sudden cardiac death in patients with chronic kidney disease (CKD). To explored the possible mechanism of CKD-related ventricular arrhythmias, a CKD rat model was created, and indoxyl sulfate (IS) was further used in vivo and in vitro. This project used the following methods: patch clamp, electrocardiogram, and some molecular biology experimental techniques. IS was found to be significantly elevated in the serum of CKD rats. Interestingly, the expression levels of the fast transient outward potassium current\u2013related (I\n                    <jats:sub>to,f<\/jats:sub>\n                    -related) proteins (Kv4.2, Kv4.3, and KChIP2) in the heart of CKD rats and rats treated with IS decreased. IS dose-dependently reduced I\n                    <jats:sub>to,f<\/jats:sub>\n                    density, accompanied by the decreases in Kv4.2, Kv4.3, and KChIP2 proteins in vitro. IS also prolonged the action potential duration and QT interval, and paroxysmal ventricular tachycardia could be induced by IS. In-depth studies have shown that ROS\/p38MAPK, ROS\u2013p44\/42 MAPK, and NF-\u03baB signaling pathways play key roles in the reduction of I\n                    <jats:sub>to,f<\/jats:sub>\n                    density and I\n                    <jats:sub>to,f<\/jats:sub>\n                    -related proteins caused by IS. These data suggest that IS reduces I\n                    <jats:sub>to,f<\/jats:sub>\n                    -related proteins and I\n                    <jats:sub>to,f<\/jats:sub>\n                    density by activating ROS\/MAPK and NF-\u03baB signaling pathways, and the action potential duration and QT interval are subsequently prolonged, which contributes to increasing the susceptibility to arrhythmia in CKD.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.145475","type":"journal-article","created":{"date-parts":[[2022,2,7]],"date-time":"2022-02-07T14:00:56Z","timestamp":1644242456000},"source":"Crossref","is-referenced-by-count":28,"title":["Indoxyl sulfate reduces Ito,f by activating ROS\/MAPK and NF-\u03baB signaling pathways"],"prefix":"10.1172","volume":"7","author":[{"given":"Jing","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Cardiology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongxia","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Cardiology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chi","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Cardiology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yafeng","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Dushu Lake Hospital Affiliated to Soochow University, Suzhou, Jiangsu, China."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"232","published-online":{"date-parts":[[2022,2,8]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1038\/ki.2011.368"},{"key":"B2","unstructured":"USRDS Annual Data Report. 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