{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T05:59:25Z","timestamp":1792648765954,"version":"4.5.0"},"reference-count":13,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"17","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2022,9,6]]},"abstract":"<jats:sec sec-type=\"background\" xml:lang=\"en\">\n            <jats:title>Background<\/jats:title>\n            <jats:p xml:lang=\"en\">The pathways of diastolic dysfunction and heart failure with preserved ejection fraction driven by lipotoxicity with metabolic syndrome are incompletely understood. Thus, there is an urgent need for animal models that accurately mimic the metabolic and cardiovascular phenotypes of this phenogroup for mechanistic studies.<\/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              Hyperlipidemia was induced in WT\u2010129 mice by 4\u2009weeks of biweekly poloxamer\u2010407 intraperitoneal injections with or without a single intravenous injection of adeno\u2010associatedvirus 9\u2013cardiac troponin T\u2013low\u2010density lipoprotein receptor (n=31), or single intravenous injection with adeno\u2010associatedvirus 9\u2013cardiac troponin T\u2013low\u2010density lipoprotein receptor alone (n=10). Treatment groups were compared with untreated or placebo controls (n=37). Echocardiography, blood pressure, whole\u2010body plethysmography, ECG telemetry, activity wheel monitoring, and biochemical and histological changes were assessed at 4 to 8\u2009weeks. At 4\u2009weeks, double treatment conferred diastolic dysfunction, preserved ejection fraction, and increased left ventricular wall thickness. Blood pressure and whole\u2010body plethysmography results were normal, but respiration decreased at 8\u2009weeks (\n              <jats:italic>P<\/jats:italic>\n              &lt;0.01). ECG and activity wheel monitoring, respectively, indicated heart block and decreased exercise activity (\n              <jats:italic>P<\/jats:italic>\n              &lt;0.001). Double treatment promoted elevated myocardial lipids including total cholesterol, fibrosis, increased wet\/dry lung (\n              <jats:italic>P<\/jats:italic>\n              &lt;0.001) and heart weight\/body weight (\n              <jats:italic>P<\/jats:italic>\n              &lt;0.05). Xanthelasma, ascites, and cardiac ischemia were evident in double and single (p407) groups. Sudden death occurred between 6 and 12\u2009weeks in double and single (p407) treatment groups.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p xml:lang=\"en\">We present a novel model of heart failure with preserved ejection fraction driven by dyslipidemia where mice acquire diastolic dysfunction, arrhythmia, cardiac hypertrophy, fibrosis, pulmonary congestion, exercise intolerance, and preserved ejection fraction in the absence of obesity, hypertension, kidney disease, or diabetes. The model can be applied to dissect pathways of metabolic syndrome that drive diastolic dysfunction in this lipotoxicity\u2010mediated heart failure with preserved ejection fraction phenogroup mimic.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/jaha.122.027216","type":"journal-article","created":{"date-parts":[[2022,9,3]],"date-time":"2022-09-03T09:20:35Z","timestamp":1662196835000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":11,"title":["Mouse Model of Heart Failure With Preserved Ejection Fraction Driven by Hyperlipidemia and Enhanced Cardiac Low\u2010Density Lipoprotein Receptor Expression"],"prefix":"10.1161","volume":"11","author":[{"given":"Monique","family":"Williams","sequence":"first","affiliation":[{"name":"Department of Medicine Division of Cardiology University of Miami Leonard M. Miller School of Medicine Miami FL"},{"name":"Interdisciplinary Stem Cell Institute University of Miami Leonard M. Miller School of Medicine Miami FL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jose Manuel Condor","family":"Capcha","sequence":"additional","affiliation":[{"name":"Department of Medicine Division of Cardiology University of Miami Leonard M. Miller School of Medicine Miami FL"},{"name":"Interdisciplinary Stem Cell Institute University of Miami Leonard M. Miller School of Medicine Miami FL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camila Iansen","family":"Irion","sequence":"additional","affiliation":[{"name":"Department of Medicine Division of Cardiology University of Miami Leonard M. Miller School of Medicine Miami FL"},{"name":"Interdisciplinary Stem Cell Institute University of Miami Leonard M. Miller School of Medicine Miami FL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grace","family":"Seo","sequence":"additional","affiliation":[{"name":"Department of Medical Education University of Miami Leonard M. Miller School of Medicine Miami FL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guerline","family":"Lambert","sequence":"additional","affiliation":[{"name":"Department of Medicine Division of Cardiology University of Miami Leonard M. Miller School of Medicine Miami FL"},{"name":"Interdisciplinary Stem Cell Institute University of Miami Leonard M. Miller School of Medicine Miami FL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0410-2269","authenticated-orcid":false,"given":"Ali","family":"Kamiar","sequence":"additional","affiliation":[{"name":"Interdisciplinary Stem Cell Institute University of Miami Leonard M. Miller School of Medicine Miami FL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keyvan","family":"Yousefi","sequence":"additional","affiliation":[{"name":"Interdisciplinary Stem Cell Institute University of Miami Leonard M. Miller School of Medicine Miami FL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosemeire","family":"Kanashiro\u2010Takeuchi","sequence":"additional","affiliation":[{"name":"Interdisciplinary Stem Cell Institute University of Miami Leonard M. Miller School of Medicine Miami FL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lauro","family":"Takeuchi","sequence":"additional","affiliation":[{"name":"Interdisciplinary Stem Cell Institute University of Miami Leonard M. Miller School of Medicine Miami FL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ali G.","family":"Saad","sequence":"additional","affiliation":[{"name":"Departments of Pathology and Pediatrics University of Miami Leonard M. Miller School of Medicine Miami FL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Armando","family":"Mendez","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Diabetes and Metabolism Diabetes Research Institute University of Miami Leonard M. Miller School of Medicine Miami FL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keith A.","family":"Webster","sequence":"additional","affiliation":[{"name":"Cullen Eye Institute Baylor College of Medicine Houston TX"},{"name":"Integene International LLC Houston TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9802-1851","authenticated-orcid":false,"given":"Jeffrey J.","family":"Goldberger","sequence":"additional","affiliation":[{"name":"Department of Medicine Division of Cardiology University of Miami Leonard M. Miller School of Medicine Miami FL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshua M.","family":"Hare","sequence":"additional","affiliation":[{"name":"Interdisciplinary Stem Cell Institute University of Miami Leonard M. Miller School of Medicine Miami FL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2095-9326","authenticated-orcid":false,"given":"Lina A.","family":"Shehadeh","sequence":"additional","affiliation":[{"name":"Department of Medicine Division of Cardiology University of Miami Leonard M. Miller School of Medicine Miami FL"},{"name":"Interdisciplinary Stem Cell Institute University of Miami Leonard M. Miller School of Medicine Miami FL"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41569-020-00480-6"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIR.0000000000000973"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1042\/CS20210127"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.120.050498"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.3389\/fcvm.2020.610282"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23126674"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00535.2020"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12944-016-0186-7"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1002\/ejhf.1970"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.15386\/cjmed-751"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.116.022362"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1097\/IOP.0000000000002070"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-019-1100-z"}],"container-title":["Journal of the American Heart Association"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/JAHA.122.027216","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,13]],"date-time":"2024-05-13T12:58:40Z","timestamp":1715605120000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/JAHA.122.027216"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,9,6]]},"references-count":13,"journal-issue":{"issue":"17","published-print":{"date-parts":[[2022,9,6]]}},"alternative-id":["10.1161\/JAHA.122.027216"],"URL":"https:\/\/doi.org\/10.1161\/jaha.122.027216","relation":{},"ISSN":["2047-9980"],"issn-type":[{"value":"2047-9980","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,9,6]]},"assertion":[{"value":"2022-06-20","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-07-26","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-09-03","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e027216"}}