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

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. T 3 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 T 3 -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 β 1 -AR signaling is crucial for TiCH.