{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,4]],"date-time":"2026-07-04T02:47:14Z","timestamp":1783133234522,"version":"3.54.6"},"reference-count":43,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"1","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2019,1,8]]},"abstract":"\n Background<\/jats:title>\n The molecular mechanisms through which high\u2010demand pacing induce myocardial dysfunction remain unclear.<\/jats:p>\n <\/jats:sec>\n \n Methods and Results<\/jats:title>\n \n We created atrioventricular block in pigs using dependent right ventricular septal pacing for 6\u00a0months. Echocardiography was performed to evaluate dyssynchrony between pacing (n=6) and sham control (n=6) groups. Microarray and enrichment analyses were used to identify differentially expressed genes (\n DEG<\/jats:styled-content>\n s) in the left ventricular (\n LV<\/jats:styled-content>\n ) myocardium between pacing and sham control groups. Histopathological and protein changes were also analyzed and an A cell pacing model was also performed. Pacing significantly increased mechanical dyssynchrony. Enrichment analysis using Ingenuity Pathway Analysis and the activation z\u2010score analysis method demonstrated that there were 5\n DEG<\/jats:styled-content>\n s (\n ABCA<\/jats:styled-content>\n 1,\n APOD<\/jats:styled-content>\n ,\n CLU<\/jats:styled-content>\n ,\n LY<\/jats:styled-content>\n 96, and\n SERPINF<\/jats:styled-content>\n 1) in the\n LV<\/jats:styled-content>\n septum (z\u2010score=\u22120.447) and 5\n DEG<\/jats:styled-content>\n s (\n APOD<\/jats:styled-content>\n ,\n CLU<\/jats:styled-content>\n ,\n LY<\/jats:styled-content>\n 96,\n MSR<\/jats:styled-content>\n 1, and\n SERPINF<\/jats:styled-content>\n 1) in the\n LV<\/jats:styled-content>\n free wall (z\u2010score=\u22121.000) inhibited the liver X receptor\/retinoid X receptor (\n LXR<\/jats:styled-content>\n \/\n RXR<\/jats:styled-content>\n ) pathway, and 4\n DEG<\/jats:styled-content>\n s (\n ACTA<\/jats:styled-content>\n 2,\n MYL<\/jats:styled-content>\n 1,\n PPP<\/jats:styled-content>\n 2R3A, and\n SNAI<\/jats:styled-content>\n 2) activated the integrin\u2010linked kinase (\n ILK<\/jats:styled-content>\n ) pathway in the\n LV<\/jats:styled-content>\n septum (z\u2010score=1.000). The pacing group had a larger cell size, higher degree of myolysis and fibrosis, and increased expression of intracellular lipid, inflammatory cytokines, and apoptotic markers than the sham control group. The causal relationships between pacing and\n DEG<\/jats:styled-content>\n s related to\n LXR<\/jats:styled-content>\n \/\n RXR<\/jats:styled-content>\n and\n ILK<\/jats:styled-content>\n pathways, apoptosis, fibrosis, and lipid expression after pacing were confirmed in the cell pacing model. Luciferase reporter assay in the cell pacing model also supported inhibition of the\n LXR<\/jats:styled-content>\n pathway by pacing.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n Right ventricular septal\u2010dependent pacing was associated with persistent\n LV<\/jats:styled-content>\n dyssynchrony\u2013induced cardiomyopathy through inhibition of the\n LXR<\/jats:styled-content>\n \/\n RXR<\/jats:styled-content>\n pathway.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1161\/jaha.118.009146","type":"journal-article","created":{"date-parts":[[2019,1,5]],"date-time":"2019-01-05T10:00:17Z","timestamp":1546682417000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":15,"title":["Liver X Receptor\/Retinoid X Receptor Pathway Plays a Regulatory Role in Pacing\u2010Induced Cardiomyopathy"],"prefix":"10.1161","volume":"8","author":[{"given":"Yu\u2010Sheng","family":"Lin","sequence":"first","affiliation":[{"name":"Division of Cardiology Chang Gung Memorial Hospital Chiayi Taiwan"},{"name":"Graduate Institute of Clinical Medical Sciences College of Medicine Chang Gung University Taoyuan Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tzu\u2010Hao","family":"Chang","sequence":"additional","affiliation":[{"name":"Graduate Institute of Biomedical Informatics Taipei Medical University Taipei Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chung\u2010Sheng","family":"Shi","sequence":"additional","affiliation":[{"name":"Graduate Institute of Clinical Medical Sciences College of Medicine Chang Gung University Taoyuan Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi\u2010Zhen","family":"Wang","sequence":"additional","affiliation":[{"name":"Division of Cardiology Department of Internal Medicine Kaohsiung Chang Gung Memorial Hospital Chang Gung University College of Medicine Kaohsiung Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wan\u2010Chun","family":"Ho","sequence":"additional","affiliation":[{"name":"Division of Cardiology Department of Internal Medicine Kaohsiung Chang Gung Memorial Hospital Chang Gung University College of Medicine Kaohsiung Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hsien\u2010Da","family":"Huang","sequence":"additional","affiliation":[{"name":"The Warshel Institute of Computational Biology School of Science and Technology The Chinese University of Hong Kong Shenzhen China"},{"name":"Department of Biological Science and Technology National Chiao Tung University Hsinchu Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shih\u2010Tai","family":"Chang","sequence":"additional","affiliation":[{"name":"Division of Cardiology Chang Gung Memorial Hospital Chiayi 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