Activity of Cardiomyocyte Type 3 Deiodinase After Myocardial Infarction Influences Cardiac Recovery in Females

Authors

Maigen Bethea, Department of Pediatrics, Section of Nutrition, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
Tyler Cook, Department of Pediatrics, Section of Nutrition, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
Preston Stafford, Division of Cardiology, Department of Medicine, University of Colorado School of Medicine (UCSOM), Aurora, CO 80045, USA.
Leslie Knaub, Division of Endocrinology, Department of Medicine, University of Colorado School of Medicine (UCSOM), Aurora, CO 80045, USA.
Maria Elena Martinez, Center for Molecular Medicine, MaineHealth Institute for Research, MaineHealth, Scarborough, ME, United States.
Bjoern Schniedewind, Department of Anesthesiology, University of Colorado School of Medicine, Aurora, Colorado; and iC42 Clinical Research and Development Clinical Mass Spectrometry Service Center, University of Colorado School of Medicine, Aurora, Colorado.
Uwe Christians, Department of Anesthesiology, University of Colorado School of Medicine, Aurora, Colorado; and iC42 Clinical Research and Development Clinical Mass Spectrometry Service Center, University of Colorado School of Medicine, Aurora, Colorado.
Jasmine Jay Hendrix, Department of Pediatrics, Section of Nutrition, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
Arturo Hernandez, Center for Molecular Medicine, MaineHealth Institute for Research, MaineHealth, Scarborough, ME, United States.Follow

Document Type

Article

Publication Date

12-12-2025

Institution/Department

Center for Molecular Medicine

Journal Title

Endocrinology

Abstract

Thyroid hormone (TH) is essential for cardiovascular function, and women are disproportionately affected by TH disorders and experience worse outcomes following myocardial infarction (MI). 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 (Dio3ΔHeart) mice, we investigated how impaired TH inactivation influences cardiac function and mitochondrial respiration. We also examined DIO3 mRNA expression, which encodes the D3 enzyme, in left ventricular (LV) tissue from human donors with non-failing (NF) hearts or ischemic cardiomyopathy (ICM). Four weeks post-MI, wild-type female mice exhibited sustained cardiac D3 activity, which effectively limited triiodothyronine (T3) levels in the left ventricle. In contrast, Dio3ΔHeart females, lacking cardiomyocyte D3, showed impaired systolic recovery, elevated LV T4 and T3 levels, and reduced fatty acid-supported mitochondrial respiration, effects not observed in Dio3ΔHeart 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.

Recommended Citation

Bethea, Maigen; Cook, Tyler; Stafford, Preston; Knaub, Leslie; Martinez, Maria Elena; Schniedewind, Bjoern; Christians, Uwe; Hendrix, Jasmine Jay; and Hernandez, Arturo, "Activity of Cardiomyocyte Type 3 Deiodinase After Myocardial Infarction Influences Cardiac Recovery in Females" (2025). MaineHealth Maine Medical Center. 4244.
https://knowledgeconnection.mainehealth.org/mmc/4244