Thyroid hormone induces restrictive cardiomyopathy in 1-adrenoceptor knockout mice

The purpose of this study was to characterize the role of beta(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 mgkg(-1)day(-1) for 10 days in beta 1-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). beta 1-KOT3 exhibited lower LVEDD and higher relative IVSTd versus beta 1-KOsal, the lowest levels of ejection fraction, and the highest levels of cardiomyocyte diameter (p < 0.05). Cardiac ANP levels decreased in WTT3 versus beta 1-KOT3 (p < 0.05). Cardiac ACE expression was increased in T-3-treated groups (p < 0.05). Phosphorylated-p38 MAPK levels were higher in WTT3 versus WTsal or beta 1-KOT3, p-4EBP1 was elevated in beta 1-KO animals, and p-ERK1/2 was up-regulated in beta 1-KOT3. These findings suggest that beta(1)-AR signaling is crucial for TiCH.