{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T05:04:24Z","timestamp":1774933464049,"version":"3.50.1"},"reference-count":60,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,2,22]],"date-time":"2024-02-22T00:00:00Z","timestamp":1708560000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Thyroid hormones (THs) are known to have various effects on the cardiovascular system. However, the impact of TH levels on preexisting cardiac diseases is still unclear. Pressure overload due to arterial hypertension or aortic stenosis and aging are major risk factors for the development of structural and functional abnormalities and subsequent heart failure. Here, we assessed the sensitivity to altered TH levels in aged mice with maladaptive cardiac hypertrophy and cardiac dysfunction induced by transverse aortic constriction (TAC).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Mice at the age of 12 months underwent TAC and received T4 or anti-thyroid medication in drinking water over the course of 4 weeks after induction of left ventricular pressure overload.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>T4 excess or deprivation in older mice had no or only very little impact on cardiac function (fractional shortening), cardiac remodeling (cardiac wall thickness, heart weight, cardiomyocyte size, apoptosis, and interstitial fibrosis), and mortality. This is surprising because T4 excess or deprivation had significantly changed the outcome after TAC in young 8-week-old mice. Comparing the gene expression of deiodinases (Dio) 2 and 3 and TH receptor alpha (TR\u03b1) 1 and the dominant-negative acting isoform TR\u03b12 between young and aged mice revealed that aged mice exhibited a higher expression of TR\u03b12 and Dio3, while expression of Dio2 was reduced compared with young mice. These changes in Dio2 and 3 expressions might lead to reduced TH availability in the hearts of 12-month-old mice accompanied by reduced TR\u03b1 action due to higher TR\u03b12.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>In summary, our study shows that low and high TH availability have little impact on cardiac function and remodeling in older mice with preexisting pressure-induced cardiac damage. This observation seems to be the result of an altered expression of deiodinases and TR\u03b1 isoforms, thus suggesting that even though cardiovascular risk is increasing with age, the response to TH stress may be dampened in certain conditions.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fendo.2024.1339741","type":"journal-article","created":{"date-parts":[[2024,2,21]],"date-time":"2024-02-21T23:51:56Z","timestamp":1708559516000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Cardiac recovery from pressure overload is not altered by thyroid hormone status in old mice"],"prefix":"10.3389","volume":"15","author":[{"given":"Helena","family":"Kerp","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Janina","family":"Gassen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Susanne Camilla","family":"Grund","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Georg Sebastian","family":"H\u00f6nes","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefanie","family":"D\u00f6rr","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jens","family":"Mittag","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nina","family":"H\u00e4rting","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Frank","family":"Kaiser","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lars Christian","family":"Moeller","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kristina","family":"Lorenz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dagmar","family":"F\u00fchrer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2024,2,22]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1093\/eurjpc\/zwaa147","article-title":"Burden of heart failure and underlying causes in 195 countries and territories from 1990 to 2017","volume":"28","author":"Bragazzi","year":"2021","journal-title":"Eur J Prev Cardiol"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1007\/s10741-008-9125-7","article-title":"Cardiac hypertrophy and thyroid hormone signaling","volume":"15","author":"Dillmann","year":"2010","journal-title":"Review Heart failure Rev"},{"key":"B3","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1007\/s10741-010-9185-3","article-title":"New insights into the role of thyroid hormone in cardiac remodeling: time to reconsider","volume":"16","author":"Pantos","year":"2011","journal-title":"Heart Fail Rev"},{"key":"B4","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1038\/nrcardio.2016.174","article-title":"Thyroid hormones and cardiovascular disease","volume":"14","author":"Jabbar","year":"2017","journal-title":"Nat Rev Cardiol"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2018.02.045","article-title":"Thyroid hormones and cardiovascular function and diseases","volume":"71","author":"Razvi","year":"2018","journal-title":"J Am Coll Cardiol"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.2478\/enr-2022-0033","article-title":"Interplay between cardiovascular and thyroid dysfunctions: A review of clinical implications and management strategies","volume":"56","author":"Debmalya","year":"2022","journal-title":"Endocr Regul"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1007\/s12020-022-02982-4","article-title":"Thyroid disorders and cardiovascular manifestations: an update","volume":"75","author":"Paschou","year":"2022","journal-title":"Endocrine"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.118.036859","article-title":"Thyroid and cardiovascular disease: research agenda for enhancing knowledge, prevention, and treatment","volume":"139","author":"Cappola","year":"2019","journal-title":"Circulation"},{"key":"B9","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1159\/000490911","article-title":"Thyroid function changes in the elderly and their relationship to cardiovascular health: A mini-review","volume":"65","author":"Barbesino","year":"2019","journal-title":"Gerontology"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2012-2481","article-title":"Longitudinal changes in thyroid function in the oldest old and survival: the cardiovascular health study all-stars study","volume":"97","author":"Waring","year":"2012","journal-title":"J Clin Endocrinol Metab"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1161\/CIR.0000000000000366","article-title":"Executive summary: heart disease and stroke statistics\u20132016 update: A report from the American heart association","volume":"133","author":"Mozaffarian","year":"2016","journal-title":"Circulation"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1016\/j.scr.2014.07.001","article-title":"Thyroid hormone action in postnatal heart development","volume":"13","author":"Li","year":"2014","journal-title":"Stem Cell Res"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9343(90)90530-q","article-title":"Biochemical basis of thyroid hormone action in the heart","volume":"88","author":"Dillmann","year":"1990","journal-title":"Am J Med"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1210\/er.2003-0033","article-title":"Thyroid hormone action in the heart","volume":"26","author":"Kahaly","year":"2005","journal-title":"Endocr Rev"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1006\/jmcc.1998.0900","article-title":"Thyroid hormone control of contraction and the Ca(2+)-ATPase\/phospholamban complex in adult rat ventricular myocytes","volume":"31","author":"Holt","year":"1999","journal-title":"J Mol Cell Cardiol"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.75.2.245","article-title":"Thyroid hormone-induced alterations in phospholamban protein expression. Regulatory effects on sarcoplasmic reticulum Ca2+ transport and myocardial relaxation","volume":"75","author":"Kiss","year":"1994","journal-title":"Circ Res"},{"key":"B17","doi-asserted-by":"publisher","first-page":"3312","DOI":"10.1038\/s41467-023-38960-1","article-title":"Resistance to thyroid hormone induced tachycardia in RTHalpha syndrome","volume":"14","author":"Dore","year":"2023","journal-title":"Nat Commun"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2016.06.001","article-title":"Physiological and pathological cardiac hypertrophy","volume":"97","author":"Shimizu","year":"2016","journal-title":"J Mol Cell Cardiol"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.106.678326","article-title":"Thyroid disease and the heart","volume":"116","author":"Klein","year":"2007","journal-title":"Circulation"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.01000.2004","article-title":"Thyroid hormones induce unique and potentially beneficial changes in cardiac myocyte shape in hypertensive rats near heart failure","volume":"288","author":"Thomas","year":"2005","journal-title":"Am J Physiol Heart Circ Physiol"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1161\/circulationaha.109.917922","article-title":"Thyroid replacement therapy and heart failure","volume":"122","author":"Gerdes","year":"2010","journal-title":"Circulation"},{"key":"B22","article-title":"Regional changes in myocyte size and number in propranolol-treated hyperthyroid rats","volume":"57","author":"Gerdes","year":"1987","journal-title":"Lab Invest"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1016\/j.vph.2009.10.004","article-title":"Thyroid hormone and chronically unloaded hearts","volume":"52","author":"Ito","year":"2010","journal-title":"Vascul Pharmacol"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1161\/01.res.71.4.831","article-title":"Decreased collagen gene expression and absence of fibrosis in thyroid hormone-induced myocardial hypertrophy. Response of cardiac fibroblasts to thyroid hormone in vitro","volume":"71","author":"Yao","year":"1992","journal-title":"Circ Res"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.3389\/fcvm.2021.683522","article-title":"Protective effects of thyroid hormone deprivation on progression of maladaptive cardiac hypertrophy and heart failure","volume":"8","author":"Kerp","year":"2021","journal-title":"Front Cardiovasc Med"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.3390\/cells12131780","article-title":"The microenvironment of the pathogenesis of cardiac hypertrophy","volume":"12","author":"Bazgir","year":"2023","journal-title":"Cells"},{"key":"B27","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1172\/jci62839","article-title":"Signaling effectors underlying pathologic growth and remodeling of the heart","volume":"123","author":"van Berlo","year":"2013","journal-title":"J Clin Invest"},{"key":"B28","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1038\/nm.1893","article-title":"A new type of ERK1\/2 autophosphorylation causes cardiac hypertrophy","volume":"15","author":"Lorenz","year":"2009","journal-title":"Nat Med"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3972","article-title":"Cardiac RKIP induces a beneficial beta-adrenoceptor-dependent positive inotropy","volume":"21","author":"Schmid","year":"2015","journal-title":"Nat Med"},{"key":"B30","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1007\/s12020-016-1020-8","article-title":"Efficacy of protocols for induction of chronic hyperthyroidism in male and female mice","volume":"54","author":"Engels","year":"2016","journal-title":"Endocrine"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1093\/gerona\/glz040","article-title":"Aging alters phenotypic traits of thyroid dysfunction in male mice with divergent effects on complex systems but preserved thyroid hormone action in target organs","volume":"74","author":"Engels","year":"2019","journal-title":"Journals Gerontol Ser A Biol Sci Med Sci"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00019.2002","article-title":"Thyroid hormone and cardiac function in mice deficient in thyroid hormone receptor-alpha or -beta: an echocardiograph study. Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S","volume":"283","author":"Weiss","year":"2002","journal-title":"Am J Physiol Endocrinol Metab"},{"key":"B33","doi-asserted-by":"publisher","first-page":"596","DOI":"10.1007\/s12020-019-02078-6","article-title":"Age effect on thyroid hormone brain response in male mice","volume":"66","author":"Kerp","year":"2019","journal-title":"Endocrine"},{"key":"B34","doi-asserted-by":"publisher","first-page":"1733","DOI":"10.1038\/s41467-020-15505-4","article-title":"Interference with ERK-dimerization at the nucleocytosolic interface targets pathological ERK1\/2 signaling without cardiotoxic side-effects","volume":"11","author":"Tomasovic","year":"2020","journal-title":"Nat Commun"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1089\/thy.2018.0377","article-title":"Aging is associated with low thyroid state and organ specific sensitivity to thyroxine","volume":"29","author":"Rakov","year":"2019","journal-title":"Thyroid"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1530\/EJE-07-0318","article-title":"Thyroid hormone is a critical determinant of myocardial performance in patients with heart failure: potential therapeutic implications","volume":"157","author":"Pantos","year":"2007","journal-title":"Eur J Endocrinol"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.116.305381","article-title":"Getting to the heart of the matter: new insights into cardiac fibrosis","volume":"116","author":"Leask","year":"2015","journal-title":"Circ Res"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1054\/jcaf.2001.24609","article-title":"B-type natriuretic peptide levels: a potential novel \"white count\" for congestive heart failure","volume":"7","author":"Maisel","year":"2001","journal-title":"J Card Fail"},{"key":"B39","doi-asserted-by":"publisher","first-page":"86A","DOI":"10.1016\/0735-1097(93)90468-g","article-title":"Atrial natriuretic peptide in heart failure","volume":"22","author":"Brandt","year":"1993","journal-title":"J Am Coll Cardiol"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2022.777284","article-title":"Differential mRNA expression and circular RNA-based competitive endogenous RNA networks in the three stages of heart failure in transverse aortic constriction mice","volume":"13","author":"Li","year":"2022","journal-title":"Front Physiol"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1016\/s0195-668x(02)00829-1","article-title":"Molecular determinants of myocardial hypertrophy and failure: alternative pathways for beneficial and maladaptive hypertrophy","volume":"24","author":"Lips","year":"2003","journal-title":"Eur Heart J May"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0149941","article-title":"Tissue-specific suppression of thyroid hormone signaling in various mouse models of aging","volume":"11","author":"Visser","year":"2016","journal-title":"PloS One"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1161\/01.hyp.17.3.369","article-title":"Effect of age on coronary circulation after imposition of pressure-overload in rats","volume":"17","author":"Isoyama","year":"1991","journal-title":"Hypertension"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1161\/01.res.61.3.337","article-title":"Effect of age on the development of cardiac hypertrophy produced by aortic constriction in the rat","volume":"61","author":"Isoyama","year":"1987","journal-title":"Circ Res"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1023\/A:1013701923065","article-title":"Acute and chronic adaptation to hemodynamic overload and ischemia in the aged heart","volume":"7","author":"Isoyama","year":"2002","journal-title":"Heart Fail Rev"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0015187","article-title":"Bone marrow support of the heart in pressure overload is lost with aging","volume":"5","author":"Sopko","year":"2010","journal-title":"PloS One"},{"key":"B47","first-page":"72","article-title":"Aging is protective against pressure overload cardiomyopathy via adaptive extracellular matrix remodeling","volume":"7","author":"Geng","year":"2017","journal-title":"Am J Cardiovasc Dis"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1093\/geronj\/28.3.293","article-title":"Effect of age on thyroxine-induced cardiac hypertrophy in mice","volume":"28","author":"Florini","year":"1973","journal-title":"J Gerontol"},{"key":"B49","doi-asserted-by":"publisher","first-page":"6998","DOI":"10.3390\/ijms23136998","article-title":"TRalpha2 \u2013an untuned second fiddle or fine-tuning thyroid hormone action","volume":"23","author":"H\u00f6nes","year":"2022","journal-title":"Int J Mol Sci"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1016\/s0024-3205(96)00539-5","article-title":"Cardiac nuclear hormone receptor mRNA in heart failure in man","volume":"59","author":"Sylv\u00e9n","year":"1996","journal-title":"Life Sci"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1161\/01.cir.103.8.1089","article-title":"Signaling pathways responsible for fetal gene induction in the failing human heart: evidence for altered thyroid hormone receptor gene expression","volume":"103","author":"Kinugawa","year":"2001","journal-title":"Circulation"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1210\/me.2004-0503","article-title":"Thyroid hormone induces cardiac myocyte hypertrophy in a thyroid hormone receptor alpha1-specific manner that requires TAK1 and p38 mitogen-activated protein kinase","volume":"19","author":"Kinugawa","year":"2005","journal-title":"Mol Endocrinol"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1210\/en.2003-1670","article-title":"The metabolic and cardiovascular effects of hyperthyroidism are largely independent of beta-adrenergic stimulation","volume":"145","author":"Bachman","year":"2004","journal-title":"Endocrinology"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1089\/thy.2019.0705","article-title":"Central hypothyroidism impairs heart rate stability and prevents thyroid hormone-induced cardiac hypertrophy and pyrexia","volume":"30","author":"Herrmann","year":"2020","journal-title":"Thyroid"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.1210\/clinem\/dgac417","article-title":"Effect of levothyroxine supplementation on the cardiac morphology and function in patients with subclinical hypothyroidism: A systematic review and meta-analysis","volume":"107","author":"Wang","year":"2022","journal-title":"J Clin Endocrinol Metab"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.1001\/jama.295.9.1033","article-title":"Thyroid status, cardiovascular risk, and mortality in older adults","volume":"295","author":"Cappola","year":"2006","journal-title":"Jama"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.1007\/s11010-011-1175-9","article-title":"Dose-dependent effects of thyroid hormone on post-ischemic cardiac performance: potential involvement of Akt and ERK signalings","volume":"363","author":"Mourouzis","year":"2012","journal-title":"Mol Cell Biochem"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.1089\/thy.2021.0596","article-title":"Effects of acute triiodothyronine treatment in patients with anterior myocardial infarction undergoing primary angioplasty: evidence from a pilot randomized clinical trial (ThyRepair study)","volume":"32","author":"Pantos","year":"2022","journal-title":"Thyroid"},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2020.9389","article-title":"Effect of levothyroxine on left ventricular ejection fraction in patients with subclinical hypothyroidism and acute myocardial infarction: A randomized clinical trial","volume":"324","author":"Jabbar","year":"2020","journal-title":"Jama"},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00168.2010","article-title":"Thyroid hormone inhibits ERK phosphorylation in pressure overload-induced hypertrophied mouse hearts through a receptor-mediated mechanism","volume":"299","author":"Suarez","year":"2010","journal-title":"Am J Physiol Cell Physiol"}],"container-title":["Frontiers in Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2024.1339741\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,2,21]],"date-time":"2024-02-21T23:52:04Z","timestamp":1708559524000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2024.1339741\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,2,22]]},"references-count":60,"alternative-id":["10.3389\/fendo.2024.1339741"],"URL":"https:\/\/doi.org\/10.3389\/fendo.2024.1339741","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2023.11.17.567523","asserted-by":"object"}]},"ISSN":["1664-2392"],"issn-type":[{"value":"1664-2392","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,2,22]]},"article-number":"1339741"}}