1. Thyroid hormone induces restrictive cardiomyopathy in β1-adrenoceptor knockout mice.
- Author
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da Silveira A, Seara F, Lustrino D, Mecawi A, Antunes-Rodrigues J, Kettelhut Í, Chakur-Brum P, Reis L, and Olivares E
- Subjects
- Mice, Animals, Mice, Knockout, Myocardium metabolism, Thyroid Hormones, Receptors, Adrenergic metabolism, Angiotensin II pharmacology, Cardiomyopathy, Restrictive metabolism, Cardiomyopathy, Restrictive pathology
- Abstract
The purpose of this study was to characterize the role of β
1 -AR signaling and its cross-talk between cardiac renin-angiotensin system and thyroid-hormone-induced cardiac hypertrophy. T3 was administered at 0.5 mg·kg-1 ·day-1 for 10 days in β1-KOT3 and WTT3 groups, while control groups received vehicle alone. Echocardiography and myocardial histology was performed; cardiac and serum ANGI/ANGII and ANP and cardiac levels of p-PKA, p-ERK1/2, p-p38-MAPK, p-AKT, p-4EBP1, and ACE were measured. WTT3 showed decreased IVSTd and increased LVEDD versus WTsal ( p < 0.05). β1-KOT3 exhibited lower LVEDD and higher relative IVSTd versus β1-KOsal , the lowest levels of ejection fraction, and the highest levels of cardiomyocyte diameter ( p < 0.05). Cardiac ANP levels decreased in WTT3 versus β1-KOT3 ( p < 0.05). Cardiac ACE expression was increased in T3 -treated groups ( p < 0.05). Phosphorylated-p38 MAPK levels were higher in WTT3 versus WTsal or β1-KOT3, p-4EBP1 was elevated in β1-KO animals, and p-ERK1/2 was up-regulated in β1-KOT3 . These findings suggest that β1 -AR signaling is crucial for TiCH., Competing Interests: The authors declare there are no competing interests.- Published
- 2023
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