{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T16:11:49Z","timestamp":1789747909192,"version":"4.0.1"},"reference-count":40,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"3","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2019,2,5]]},"abstract":"<jats:sec xml:lang=\"en\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p xml:lang=\"en\">\n                      Whether chronic obstructive sleep apnea (\n                      <jats:styled-content style=\"fixed-case\">OSA<\/jats:styled-content>\n                      ) could promote epicardial adipose tissue (\n                      <jats:styled-content style=\"fixed-case\">EAT<\/jats:styled-content>\n                      ) secretion of profibrotic adipokines, and thereby contribute to atrial fibrosis, and the potential therapeutic effects of metoprolol remain unknown.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Methods and Results<\/jats:title>\n                    <jats:p xml:lang=\"en\">\n                      A chronic\n                      <jats:styled-content style=\"fixed-case\">OSA<\/jats:styled-content>\n                      canine model was established by repeatedly clamping the endotracheal tube for and then reopening it for 4\u00a0hours every other day for 12\u00a0weeks. In a metoprolol treatment group, metoprolol succinate was administered daily for 12\u00a0weeks. The\n                      <jats:styled-content style=\"fixed-case\">EAT<\/jats:styled-content>\n                      infiltration and left atrial fibrosis were examined. The expressions of adipokines secreted by\n                      <jats:styled-content style=\"fixed-case\">EAT<\/jats:styled-content>\n                      and hypoxic 3T3\u2010L1 adipocytes were detected. The changes in collagen synthesis, transforming growth factor\u2010\u03b21 expression, and cell differentiation and proliferation in cardiac fibroblasts induced by hypoxic 3T3\u2010L1 adipocyte\u2010derived conditioned medium were further analyzed. Chronic\n                      <jats:styled-content style=\"fixed-case\">OSA<\/jats:styled-content>\n                      induced infiltration of\n                      <jats:styled-content style=\"fixed-case\">EAT<\/jats:styled-content>\n                      into the left atrium.\n                      <jats:styled-content style=\"fixed-case\">OSA<\/jats:styled-content>\n                      enhanced the profibrotic effect of\n                      <jats:styled-content style=\"fixed-case\">EAT<\/jats:styled-content>\n                      on the adjacent atrial myocardium. Moreover,\n                      <jats:styled-content style=\"fixed-case\">OSA<\/jats:styled-content>\n                      induced profibrotic cytokine secretion from\n                      <jats:styled-content style=\"fixed-case\">EAT<\/jats:styled-content>\n                      . We also found that hypoxia induced adipokine secretion in cultured adipocytes, and the medium conditioned by the hypoxic adipocytes increased collagen and transforming growth factor\u2010\u03b21 protein expression and cell proliferation of cardiac fibroblasts. More importantly, metoprolol attenuated infiltration of\n                      <jats:styled-content style=\"fixed-case\">EAT<\/jats:styled-content>\n                      and alleviated the profibrotic effect of\n                      <jats:styled-content style=\"fixed-case\">EAT<\/jats:styled-content>\n                      by inhibiting adipokine secretion. Metoprolol also inhibited hypoxia\u2010induced adipokine secretion in adipocytes and thereby blocked the hypoxic adipocyte\u2013derived conditioned medium\u2013induced fibrotic response of cardiac fibroblasts.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p xml:lang=\"en\">\n                      Chronic\n                      <jats:styled-content style=\"fixed-case\">OSA<\/jats:styled-content>\n                      enhanced the profibrotic effect of\n                      <jats:styled-content style=\"fixed-case\">EAT<\/jats:styled-content>\n                      on the neighboring atrial myocardium by stimulating the secretion of profibrotic adipokines from\n                      <jats:styled-content style=\"fixed-case\">EAT<\/jats:styled-content>\n                      , which was significantly attenuated by metoprolol. This study gives insights into mechanisms underlying\n                      <jats:styled-content style=\"fixed-case\">OSA<\/jats:styled-content>\n                      \u2010induced atrial fibrillation and also provides experimental evidence for the protective effects of metoprolol.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/jaha.118.011155","type":"journal-article","created":{"date-parts":[[2019,1,26]],"date-time":"2019-01-26T05:00:31Z","timestamp":1548478831000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":21,"title":["Metoprolol Inhibits Profibrotic Remodeling of Epicardial Adipose Tissue in a Canine Model of Chronic Obstructive Sleep Apnea"],"prefix":"10.1161","volume":"8","author":[{"given":"Hui","family":"Dai","sequence":"first","affiliation":[{"name":"Department of Cardiology the First Affiliated Hospital Harbin Medical University Harbin China"},{"name":"Department of Emergency Xinhua Hospital Shanghai Jiao Tong University School of Medicine Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Yuan","sequence":"additional","affiliation":[{"name":"Department of Cardiology the First Affiliated Hospital Harbin Medical University Harbin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuangli","family":"Yin","sequence":"additional","affiliation":[{"name":"Department of Cardiology the First Affiliated Hospital Harbin Medical University Harbin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Cardiology the First Affiliated Hospital Harbin Medical University Harbin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Cardiology the First Affiliated Hospital Harbin Medical University Harbin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Cardiology the First Affiliated Hospital Harbin Medical University Harbin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiankai","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Cardiology the First Affiliated Hospital Harbin Medical University Harbin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jicheng","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Cardiology the First Affiliated Hospital Harbin Medical University Harbin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Sheng","sequence":"additional","affiliation":[{"name":"Department of Cardiology the First Affiliated Hospital Harbin Medical University Harbin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongtai","family":"Gong","sequence":"additional","affiliation":[{"name":"Department of Cardiology the First Affiliated Hospital Harbin Medical University Harbin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Cardiology the First Affiliated Hospital Harbin Medical University Harbin China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_1_2_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199304293281704"},{"key":"e_1_3_1_3_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.0000136587.68725.8E"},{"key":"e_1_3_1_4_2","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.116.004500"},{"key":"e_1_3_1_5_2","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.113.000421"},{"key":"e_1_3_1_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2014.05.077"},{"key":"e_1_3_1_7_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00395-014-0427-8"},{"key":"e_1_3_1_8_2","doi-asserted-by":"publisher","DOI":"10.1186\/1465-9921-15-54"},{"key":"e_1_3_1_9_2","first-page":"1294","article-title":"Epicardial fat and atrial fibrillation: current evidence, potential mechanisms, clinical implications, and future directions","volume":"38","author":"Wong CX","year":"2017","unstructured":"Wong CX, Ganesan AN, Selvanayagam JB. 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