{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T00:09:33Z","timestamp":1788480573723,"version":"build-2803163510"},"reference-count":26,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"2","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circ: Arrhythmia and Electrophysiology"],"published-print":{"date-parts":[[2013,4]]},"abstract":"<jats:sec>\n            <jats:title>Background\u2014<\/jats:title>\n            <jats:p>We examined the hypothesis that leptin signaling contributes to the atrial fibrosis and atrial fibrillation (AF) evoked by angiotensin II (AngII).<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods and Results\u2014<\/jats:title>\n            <jats:p>\n              Eight-week-old male CL57\/B6 (CNT) and leptin-deficient ob\/ob mice (Ob) were subcutaneously infused with AngII (2.0 mg\/kg per day). Two weeks later, transesophageal burst pacing and an electrophysiological study using isolated perfused hearts were performed. Left-atrial tissues were collected to determine interstitial fibrosis by Masson trichrome staining, and the expressions of mRNAs related to inflammatory profibrotic signals were assessed. Left-atrial fibroblasts were isolated from adult Sprague-Dawley and Zucker rats. The effects of leptin (100 ng\/mL) or AngII (100 nmol\/L) treatment were evaluated. In CNT-AngII mice, leptin expression in the left atrium was upregulated (\n              <jats:italic>P<\/jats:italic>\n              &lt;0.01). Transesophageal burst pacing induced atrial fibrillation in 88% (7\/8) of CNT-AngII mice, but not in Ob-AngII mice (0\/8;\n              <jats:italic>P<\/jats:italic>\n              &lt;0.01). In isolated perfused hearts, atrial fibrillation was induced only in CNT-AngII mice (4\/6; 67%). Interatrial conduction time was prolonged in CNT-AngII mice (\n              <jats:italic>P<\/jats:italic>\n              &lt;0.01), but not in Ob-AngII mice. The upregulation of collagen 1, collagen 3, transforming growth factor-\u03b21, \u03b1-smooth muscle actin, MCP-1, F4\/80, and RANTES mRNA, which was seen in CNT-AngII mice, was attenuated in Ob-AngII mice. In cultured Sprague-Dawley rat atrial fibroblasts, AngII treatment increased leptin expression (\n              <jats:italic>P<\/jats:italic>\n              &lt;0.01). Addition of leptin increased transforming growth factor-\u03b21, \u03b1-smooth muscle actin, MCP-1, and RANTES expressions in Sprague-Dawley rat atrial fibroblasts, but not in Zucker rat atrial fibroblasts.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions\u2014<\/jats:title>\n            <jats:p>Our results demonstrate for the first time that leptin signaling is essential for the development of atrial fibrosis and atrial fibrillation evoked by AngII.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/circep.111.000104","type":"journal-article","created":{"date-parts":[[2013,2,14]],"date-time":"2013-02-14T06:07:30Z","timestamp":1360822050000},"page":"402-409","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":80,"title":["Role of Leptin Signaling in the Pathogenesis of Angiotensin II\u2013Mediated Atrial Fibrosis and Fibrillation"],"prefix":"10.1161","volume":"6","author":[{"given":"Akira","family":"Fukui","sequence":"first","affiliation":[{"name":"From the Department of Laboratory Examination and Diagnostics (A.F., N.T., Y.T., T.S.), Department of Internal Medicine 1 (T.M., O.K., T.S., M.H.), and Department of Molecular Pathology (C.N.), Oita University Faculty of Medicine, Yufu, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naohiko","family":"Takahashi","sequence":"additional","affiliation":[{"name":"From the Department of Laboratory Examination and Diagnostics (A.F., N.T., Y.T., T.S.), Department of Internal Medicine 1 (T.M., O.K., T.S., M.H.), and Department of Molecular Pathology (C.N.), Oita University Faculty of Medicine, Yufu, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chisato","family":"Nakada","sequence":"additional","affiliation":[{"name":"From the Department of Laboratory Examination and Diagnostics (A.F., N.T., Y.T., T.S.), Department of Internal Medicine 1 (T.M., O.K., T.S., M.H.), and Department of Molecular Pathology (C.N.), Oita University Faculty of Medicine, Yufu, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takayuki","family":"Masaki","sequence":"additional","affiliation":[{"name":"From the Department of Laboratory Examination and Diagnostics (A.F., N.T., Y.T., T.S.), Department of Internal Medicine 1 (T.M., O.K., T.S., M.H.), and Department of Molecular Pathology (C.N.), Oita University Faculty of Medicine, Yufu, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Osamu","family":"Kume","sequence":"additional","affiliation":[{"name":"From the Department of Laboratory Examination and Diagnostics (A.F., N.T., Y.T., T.S.), Department of Internal Medicine 1 (T.M., O.K., T.S., M.H.), and Department of Molecular Pathology (C.N.), Oita University Faculty of Medicine, Yufu, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tetsuji","family":"Shinohara","sequence":"additional","affiliation":[{"name":"From the Department of Laboratory Examination and Diagnostics (A.F., N.T., Y.T., T.S.), Department of Internal Medicine 1 (T.M., O.K., T.S., M.H.), and Department of Molecular Pathology (C.N.), Oita University Faculty of Medicine, Yufu, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasushi","family":"Teshima","sequence":"additional","affiliation":[{"name":"From the Department of Laboratory Examination and Diagnostics (A.F., N.T., Y.T., T.S.), Department of Internal Medicine 1 (T.M., O.K., T.S., M.H.), and Department of Molecular Pathology (C.N.), Oita University Faculty of Medicine, Yufu, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masahide","family":"Hara","sequence":"additional","affiliation":[{"name":"From the Department of Laboratory Examination and Diagnostics (A.F., N.T., Y.T., T.S.), Department of Internal Medicine 1 (T.M., O.K., T.S., M.H.), and Department of Molecular Pathology (C.N.), Oita University Faculty of Medicine, Yufu, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tetsunori","family":"Saikawa","sequence":"additional","affiliation":[{"name":"From the Department of Laboratory Examination and Diagnostics (A.F., N.T., Y.T., T.S.), Department of Internal Medicine 1 (T.M., O.K., T.S., M.H.), and Department of Molecular Pathology (C.N.), Oita University Faculty of Medicine, Yufu, 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