Thyroid hormone induces restrictive cardiomyopathy in β1-adrenoceptor knockout mice.

Abstract

The purpose of this study was to characterize the role of β₁-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-KO_T3 and WT_T3 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. WT_T3 showed decreased IVST_d and increased LVEDD versus WT_sal (p < 0.05). β1-KO_T3 exhibited lower LVEDD and higher relative IVST_d versus β1-KO_sal, the lowest levels of ejection fraction, and the highest levels of cardiomyocyte diameter (p < 0.05). Cardiac ANP levels decreased in WT_T3 versus β1-KO_T3 (p < 0.05). Cardiac ACE expression was increased in T₃-treated groups (p < 0.05). Phosphorylated-p38 MAPK levels were higher in WT_T3 versus WT_sal or β1-KO_T3, p-4EBP1 was elevated in β1-KO animals, and p-ERK1/2 was up-regulated in β1-KO_T3. These findings suggest that β₁-AR signaling is crucial for TiCH.