Thyroid hormone improves function and Ca²⁺ handling in pressure overload hypertrophy. Association with increased sarcoplasmic reticulum Ca²⁺-ATPase and α-myosin heavy chain in rat hearts

We asked whether thyroid hormone (T₄) would improve heart function in left ventricular hypertrophy (LVH) induced by pressure overload (aortic banding). After banding for 10-22 wk, rats were treated with T₄ or saline for 10-14 d. Isovolumic LV pressure and cytosolic [Ca²⁺] (indo-1) were assessed in perfused hearts. Sarcoplasmic reticulum Ca²⁺-ATPase (SERCA), phospholamban, and α- and β-myosin heavy chain (MHC) proteins were assayed in homogenates of myocytes isolated from the same hearts. Of 14 banded hearts treated with saline, 8 had compensated LVH with normal function (LVH(comp)), whereas 6 had abnormal contraction, relaxation, and calcium handling (LVH(decomp)). In contrast, banded animals treated with T₄ had no myocardial dysfunction; these hearts had increased contractility, and faster relaxation and cytosolic [Ca²⁺] decline compared with LVH(comp) and LVH(decomp). Myocytes from banded hearts treated with T₄ were hypertrophied but had increased concentrations of α-MHC and SERCA proteins, similar to physiological hypertrophy induced by exercise. Thus thyroid hormone improves LV function and calcium handling in pressure overload hypertrophy, and these beneficial effects are related to changes in myocyte gene expression. Induction of physiological hypertrophy by thyroid hormone-like signaling might be a therapeutic strategy for treating cardiac dysfunction in pathological hypertrophy and heart failure.