{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T14:27:40Z","timestamp":1792506460038,"version":"4.5.0"},"reference-count":49,"publisher":"American Physiological Society","issue":"1","funder":[{"DOI":"10.13039\/100000050","name":"HHS | NIH | National Heart, Lung, and Blood Institute (NHBLI)","doi-asserted-by":"publisher","award":["R01HL140067"],"award-info":[{"award-number":["R01HL140067"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000968","name":"American Heart Association (AHA)","doi-asserted-by":"publisher","award":["17GRNT33710008"],"award-info":[{"award-number":["17GRNT33710008"]}],"id":[{"id":"10.13039\/100000968","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000066","name":"HHS | NIH | National Institute of Environmental Health Sciences (NIEHS)","doi-asserted-by":"publisher","award":["Z01-ES-101586"],"award-info":[{"award-number":["Z01-ES-101586"]}],"id":[{"id":"10.13039\/100000066","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Heart and Circulatory Physiology"],"published-print":{"date-parts":[[2019,1,1]]},"abstract":"<jats:p>\n                    The nuclear receptor retinoic acid-related orphan receptor-\u03b1 (ROR\u03b1) regulates numerous critical biological processes, including central nervous system development, lymphocyte differentiation, and lipid metabolism. ROR\u03b1 has been recently identified in the heart, but very little is known about its role in cardiac physiology. We sought to determine whether ROR\u03b1 regulates myocardial hypertrophy and cardiomyocyte survival in the context of angiotensin II (ANG II) stimulation. For in vivo characterization of the function of ROR\u03b1 in the context of pathological cardiac hypertrophy and heart failure, we used the \u201cstaggerer\u201d (ROR\u03b1\n                    <jats:sup>sg\/sg<\/jats:sup>\n                    ) mouse, which harbors a germline mutation encoding a truncated and globally nonfunctional ROR\u03b1. ROR\u03b1\n                    <jats:sup>sg\/sg<\/jats:sup>\n                    and wild-type littermate mice were infused with ANG II or vehicle for 14 days. For in vitro experiments, we overexpressed or silenced ROR\u03b1 in neonatal rat ventricular myocytes (NRVMs) and human cardiac fibroblasts exposed to ANG II. ROR\u03b1\n                    <jats:sup>sg\/sg<\/jats:sup>\n                    mice developed exaggerated myocardial hypertrophy and contractile dysfunction after ANG II treatment. In vitro gain- and loss-of-function experiments were consistent with the discovery that ROR\u03b1 inhibits ANG II-induced pathological hypertrophy and cardiomyocyte death in vivo. ROR\u03b1 directly repressed IL-6 transcription. Loss of ROR\u03b1 function led to enhanced IL-6 expression, proinflammatory STAT3 activation (phopho-STAT3 Tyr\n                    <jats:sup>705<\/jats:sup>\n                    ), and decreased mitochondrial number and function, oxidative stress, hypertrophy, and death of cardiomyocytes upon ANG II exposure. ROR\u03b1 was less abundant in failing compared with nonfailing human heart tissue. In conclusion, ROR\u03b1 protects against ANG II-mediated pathological hypertrophy and heart failure by suppressing the IL-6-STAT3 pathway and enhancing mitochondrial function.\n                  <\/jats:p>\n                  <jats:p>NEW &amp; NOTEWORTHY Mice lacking retinoic acid-related orphan receptor-\u03b1 (ROR\u03b1) develop exaggerated cardiac hypertrophy after angiotensin II infusion. Loss of ROR\u03b1 leads to enhanced IL-6 expression and NF-\u03baB nuclear translocation. ROR\u03b1 maintains mitochondrial function and reduces oxidative stress after angiotensin II. The abundance of ROR\u03b1 is reduced in failing mouse and human hearts.<\/jats:p>","DOI":"10.1152\/ajpheart.00531.2018","type":"journal-article","created":{"date-parts":[[2018,11,2]],"date-time":"2018-11-02T11:26:35Z","timestamp":1541157995000},"page":"H186-H200","source":"Crossref","is-referenced-by-count":44,"title":["The nuclear receptor ROR\u03b1 protects against angiotensin II-induced cardiac hypertrophy and heart failure"],"prefix":"10.1152","volume":"316","author":[{"given":"Ju Youn","family":"Beak","sequence":"first","affiliation":[{"name":"McAllister Heart Institute University of North Carolina School of Medicine, Chapel Hill, North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong Soon","family":"Kang","sequence":"additional","affiliation":[{"name":"Immunity, Inflammation and Disease Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North 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Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6430-8344","authenticated-orcid":false,"given":"Brian C.","family":"Jensen","sequence":"additional","affiliation":[{"name":"McAllister Heart Institute University of North Carolina School of Medicine, Chapel Hill, North Carolina"},{"name":"Division of Cardiology, University of North Carolina School of Medicine, Chapel Hill, North 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