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However, the role of sex-specific TH regulation in post-MI cardiac recovery remains poorly understood. We investigated TH homeostasis and type 3 deiodinase (D3) activity, an enzyme that inactivates TH, in male and female C57BL\/6 mice following MI. Using cardiomyocyte-specific D3-deficient (Dio3\u0394Heart) mice, we investigated how impaired TH inactivation influences cardiac function and mitochondrial respiration. We also examined DIO3 messenger RNA expression, which encodes the D3 enzyme, in left ventricular (LV) tissue from human donors with nonfailing (NF) hearts or ischemic cardiomyopathy (ICM). Four weeks post MI, wild-type female mice exhibited sustained cardiac D3 activity, which effectively limited 3,5,3\u2032-triiodothyronine (T3) levels in the LV. In contrast, Dio3\u0394Heart females, lacking cardiomyocyte D3, showed impaired systolic recovery, elevated LV thyroxine and T3 levels, and reduced fatty acid\u2013supported mitochondrial respiration, effects not observed in Dio3\u0394Heart males. Similarly, DIO3 expression was selectively upregulated in LV tissue from women with ICM, but not in men. These findings identify DIO3 as a key protective mechanism in females that limits T3-induced metabolic stress and preserves mitochondrial function after MI, revealing a sex-dependent pathway with therapeutic relevance for cardiac recovery.<\/jats:p>","DOI":"10.1210\/endocr\/bqaf181","type":"journal-article","created":{"date-parts":[[2025,12,11]],"date-time":"2025-12-11T13:09:03Z","timestamp":1765458543000},"source":"Crossref","is-referenced-by-count":0,"title":["Activity of Cardiomyocyte Type 3 Deiodinase After Myocardial Infarction Influences Cardiac Recovery in Females"],"prefix":"10.1210","volume":"167","author":[{"given":"Maigen","family":"Bethea","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Section of Nutrition, University of Colorado Anschutz Medical Campus , Aurora, CO 80045 ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tyler","family":"Cook","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Section of Nutrition, University of Colorado Anschutz Medical Campus , Aurora, CO 80045 ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Preston","family":"Stafford","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Medicine, University of Colorado School of Medicine (UCSOM) , Aurora, CO 80045 ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leslie","family":"Knaub","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Department of Medicine, University of Colorado School of Medicine (UCSOM) , Aurora, CO 80045 ,","place":["USA"]},{"name":"Department of Medicine, Rocky Mountain Regional Veterans Affairs Medical Center , Aurora, CO 80045 ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria Elena","family":"Martinez","sequence":"additional","affiliation":[{"name":"Center for Molecular Medicine, MaineHealth Institute for Research, MaineHealth, Scarborough , ME 04074 ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bjoern","family":"Schniedewind","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, University of Colorado School of Medicine , Aurora, CO 80045 ,","place":["USA"]},{"name":"iC42 Clinical Research and Development Clinical Mass Spectrometry Service Center, University of Colorado School of Medicine , Aurora, CO 80045 ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Uwe","family":"Christians","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, University of Colorado School of Medicine , Aurora, CO 80045 ,","place":["USA"]},{"name":"iC42 Clinical Research and Development Clinical Mass Spectrometry Service Center, University of Colorado School of Medicine , Aurora, CO 80045 ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jasmine Jay","family":"Hendrix","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Section of Nutrition, University of Colorado Anschutz Medical Campus , Aurora, CO 80045 ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luisa","family":"Mestroni","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Medicine, University of Colorado School of Medicine (UCSOM) , Aurora, CO 80045 ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sharon","family":"Graw","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Medicine, University of Colorado School of Medicine (UCSOM) , Aurora, CO 80045 ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anis","family":"Karimpour-Fard","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Medicine, University of Colorado School of Medicine (UCSOM) , Aurora, CO 80045 ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matthew R G","family":"Taylor","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Medicine, University of Colorado School of Medicine (UCSOM) , Aurora, CO 80045 ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ronald J","family":"Vagnozzi","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Medicine, University of Colorado School of Medicine (UCSOM) , Aurora, CO 80045 ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Arturo","family":"Hernandez","sequence":"additional","affiliation":[{"name":"Center for Molecular Medicine, MaineHealth Institute for Research, MaineHealth, Scarborough , ME 04074 ,","place":["USA"]},{"name":"Graduate School for Biomedical Science and Engineering, University of Maine , Orono, ME 04469 ,","place":["USA"]},{"name":"Department of Medicine, Tufts University School of Medicine , Boston, MA 02111 ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rebecca","family":"Scalzo","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Department of Medicine, University of Colorado School of Medicine (UCSOM) , Aurora, CO 80045 ,","place":["USA"]},{"name":"Department of Medicine, Rocky Mountain Regional Veterans Affairs Medical Center , Aurora, CO 80045 ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3669-3278","authenticated-orcid":false,"given":"Darleen","family":"A. 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