{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T01:06:02Z","timestamp":1792631162041,"version":"4.5.0"},"reference-count":50,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"7","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circ: Arrhythmia and Electrophysiology"],"published-print":{"date-parts":[[2016,7]]},"abstract":"<jats:sec>\n            <jats:title>Background\u2014<\/jats:title>\n            <jats:p>Postoperative atrial fibrillation is a frequent complication in cardiac surgery. The aberrant activation of signal transducer and activator of transcription 3 (STAT3) contributes to the pathogenesis of atrial fibrillation. MicroRNA-21 (miR-21) promotes atrial fibrosis. Recent studies support the existence of reciprocal regulation between STAT3 and miR-21. Here, we test the hypothesis that these 2 molecules might form a feedback loop that contributes to postoperative atrial fibrillation by promoting atrial fibrosis.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods and Results\u2014<\/jats:title>\n            <jats:p>A sterile pericarditis model was created using atrial surfaces dusted with sterile talcum powder in rats. The inflammatory cytokines interleukin (IL)-1\u03b2, IL-6, transforming growth factor-\u03b2, and tumor necrosis factor-\u03b1, along with STAT3 and miR-21, were highly upregulated in sterile pericarditis rats. The inhibition of STAT3 by S3I-201 resulted in miR-21 downregulation, which ameliorated atrial fibrosis and decreased the expression of the fibrosis-related genes, \u03b1-smooth muscle actin, collagen-1, and collagen-3; reduced the inhomogeneity of atrial conduction; and attenuated atrial fibrillation vulnerability. Meanwhile, treatment with antagomir-21 decreased STAT3 phosphorylation, alleviated atrial remodeling, abrogated sterile pericarditis\u2013induced inhomogeneous conduction, and prevented atrial fibrillation promotion. The culturing of cardiac fibroblasts with IL-6 resulted in progressively augmented STAT3 phosphorylation and miR-21 levels. S3I-201 blocked IL-6 induced the expression of miR-21 and fibrosis-related genes in addition to cardiac fibroblast proliferation. Transfected antagomir-21 decreased the IL-6\u2013induced cardiac fibroblast activation and STAT3 phosphorylation. The overexpression of miR-21 in cardiac fibroblasts caused the upregulation of STAT3 phosphorylation, enhanced fibrosis-related genes, and increased cell numbers.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions\u2014<\/jats:title>\n            <jats:p>Our results have uncovered a novel reciprocal loop between STAT3 and miR-21 that is activated after heart surgery and can contribute to atrial fibrillation.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/circep.115.003396","type":"journal-article","created":{"date-parts":[[2016,7,13]],"date-time":"2016-07-13T02:54:36Z","timestamp":1468378476000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":102,"title":["Signal Transducer and Activator of Transcription 3\/MicroRNA-21 Feedback Loop Contributes to Atrial Fibrillation by Promoting Atrial Fibrosis in a Rat Sterile Pericarditis Model"],"prefix":"10.1161","volume":"9","author":[{"given":"Zhengrong","family":"Huang","sequence":"first","affiliation":[{"name":"For the author affilations, please see the Appendix."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao-jun","family":"Chen","sequence":"additional","affiliation":[{"name":"For the author affilations, please see the Appendix."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheng","family":"Qian","sequence":"additional","affiliation":[{"name":"For the author affilations, please see the Appendix."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian","family":"Dong","sequence":"additional","affiliation":[{"name":"For the author affilations, please see the Appendix."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan","family":"Ding","sequence":"additional","affiliation":[{"name":"For the author affilations, please see the Appendix."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiong-feng","family":"Wu","sequence":"additional","affiliation":[{"name":"For the author affilations, please see the Appendix."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Li","sequence":"additional","affiliation":[{"name":"For the author affilations, please see the Appendix."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong-fei","family":"Wang","sequence":"additional","affiliation":[{"name":"For the author affilations, please see the Appendix."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei-hua","family":"Li","sequence":"additional","affiliation":[{"name":"For the author affilations, please see the Appendix."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiang","family":"Xie","sequence":"additional","affiliation":[{"name":"For the author affilations, please see the 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