{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T23:39:11Z","timestamp":1773272351975,"version":"3.50.1"},"reference-count":41,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2022,11,1]],"date-time":"2022-11-01T00:00:00Z","timestamp":1667260800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Deutsche Forschungsgemeinschaft","award":["SFB\/TR 296"],"award-info":[{"award-number":["SFB\/TR 296"]}]},{"name":"Deutsche Forschungsgemeinschaft","award":["SFB 1116"],"award-info":[{"award-number":["SFB 1116"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Hypothyroidism has been shown to reduce infarct size in rats, but the underlying mechanisms are unclear. We used isolated pressure-constant perfused hearts of control, hypothyroid and hyperthyroid mice and measured infarct size, functional parameters and phosphorylation of key molecules in cardioprotective signaling with matched heart rate. Compared with controls, hypothyroidism was cardioprotective, while hyperthyroidism was detrimental with enlarged infarct size. Next, we asked how thyroid hormone receptor \u03b1 (TR\u03b1) affects ischemia\/reperfusion (IR) injury. Thus, canonical and noncanonical TR\u03b1 signaling was investigated in the hearts of (i) mice lacking TR\u03b1 (TR\u03b10), (ii) with a mutation in TR\u03b1 DNA-binding domain (TR\u03b1GS) and (iii) in hyperthyroid TR\u03b10 (TR\u03b10hyper) and TR\u03b1GS mice (TR\u03b1GShyper). TR\u03b10 mouse hearts were protected against IR injury. Furthermore, infarct size was reduced in the hearts of TR\u03b1GS mice that lack canonical TR\u03b1 signaling but maintain noncanonical TR\u03b1 action. Hyperthyroidism did not increase infarct size in TR\u03b10 and TR\u03b1GS mouse hearts. These cardioprotective effects were not associated with increased phosphorylation of key proteins of RISK, SAFE and eNOS pathways. In summary, chronic hypothyroidism and the lack of canonical TR\u03b1 signaling are cardioprotective in IR injury and protection is not due to favorable changes in hemodynamics.<\/jats:p>","DOI":"10.3390\/ijms232113340","type":"journal-article","created":{"date-parts":[[2022,11,2]],"date-time":"2022-11-02T03:36:44Z","timestamp":1667360204000},"page":"13340","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Cardioprotection by Hypothyroidism Is Not Mediated by Favorable Hemodynamics\u2014Role of Canonical Thyroid Hormone Receptor Alpha Signaling"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4568-2135","authenticated-orcid":false,"given":"Janina","family":"Pape","sequence":"first","affiliation":[{"name":"Department of Endocrinology, Diabetes and Metabolism, University of Duisburg-Essen, 45122 Essen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Helena","family":"Kerp","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Diabetes and Metabolism, University of Duisburg-Essen, 45122 Essen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Helmut R.","family":"Lieder","sequence":"additional","affiliation":[{"name":"West German Heart and Vascular Center Essen, Institute for Pathophysiology, University of Essen Medical School, 45122 Essen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniela","family":"Geist","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Diabetes and Metabolism, University of Duisburg-Essen, 45122 Essen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5080-7166","authenticated-orcid":false,"given":"Georg Sebastian","family":"H\u00f6nes","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Diabetes and Metabolism, University of Duisburg-Essen, 45122 Essen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lars C.","family":"Moeller","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Diabetes and Metabolism, University of Duisburg-Essen, 45122 Essen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Petra","family":"Kleinbongard","sequence":"additional","affiliation":[{"name":"West German Heart and Vascular Center Essen, Institute for Pathophysiology, University of Essen Medical School, 45122 Essen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dagmar","family":"F\u00fchrer","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Diabetes and Metabolism, University of Duisburg-Essen, 45122 Essen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,11,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","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. 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