{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T23:17:50Z","timestamp":1791415070252,"version":"4.3.3"},"reference-count":79,"publisher":"American Society for Clinical Investigation","issue":"8","license":[{"start":{"date-parts":[[2021,4,22]],"date-time":"2021-04-22T00:00:00Z","timestamp":1619049600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000968","name":"American Heart Association","doi-asserted-by":"crossref","award":["18TPA34170575"],"award-info":[{"award-number":["18TPA34170575"]}],"id":[{"id":"10.13039\/100000968","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["R01HL134821,R01HL089847,R01HL105993,R01HD077260"],"award-info":[{"award-number":["R01HL134821,R01HL089847,R01HL105993,R01HD077260"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,4,22]]},"abstract":"<jats:p>\n                    Although low circulating levels of the vitamin A metabolite, all-\n                    <jats:italic>trans<\/jats:italic>\n                    retinoic acid (ATRA), are associated with increased risk of cardiovascular events and all-cause mortality, few studies have addressed whether cardiac retinoid levels are altered in the failing heart. Here, we showed that proteomic analyses of human and guinea pig heart failure (HF) were consistent with a decline in resident cardiac ATRA. Quantitation of the retinoids in ventricular myocardium by mass spectrometry revealed 32% and 39% ATRA decreases in guinea pig HF and in patients with idiopathic dilated cardiomyopathy (IDCM), respectively, despite ample reserves of cardiac vitamin A. ATRA (2 mg\/kg\/d) was sufficient to mitigate cardiac remodeling and prevent functional decline in guinea pig HF. Although cardiac ATRA declined in guinea pig HF and human IDCM, levels of certain retinoid metabolic enzymes diverged. Specifically, high expression of the ATRA-catabolizing enzyme, CYP26A1, in human IDCM could dampen prospects for an ATRA-based therapy. Pertinently, a pan-CYP26 inhibitor, talarozole, blunted the impact of phenylephrine on ATRA decline and hypertrophy in neonatal rat ventricular myocytes. Taken together, we submit that low cardiac ATRA attenuates the expression of critical ATRA-dependent gene programs in HF and that strategies to normalize ATRA metabolism, like CYP26 inhibition, may have therapeutic potential.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.137593","type":"journal-article","created":{"date-parts":[[2021,3,16]],"date-time":"2021-03-16T12:02:55Z","timestamp":1615896175000},"source":"Crossref","is-referenced-by-count":37,"title":["Cardiac retinoic acid levels decline in heart failure"],"prefix":"10.1172","volume":"6","author":[{"given":"Ni","family":"Yang","sequence":"first","affiliation":[{"name":"Division of Cardiology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lauren E.","family":"Parker","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianshi","family":"Yu","sequence":"additional","affiliation":[{"name":"Mass Spectrometry Center and Department of Pharmaceutical Sciences, University of Maryland School of Pharmacy, Baltimore, Maryland, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0460-0380","authenticated-orcid":true,"given":"Jace W.","family":"Jones","sequence":"additional","affiliation":[{"name":"Mass Spectrometry Center and Department of Pharmaceutical Sciences, University of Maryland School of Pharmacy, Baltimore, Maryland, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting","family":"Liu","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyriakos N.","family":"Papanicolaou","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3758-2425","authenticated-orcid":true,"suffix":"Jr.","given":"C. 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