Thyroid hormone improves function and Ca2+ handling in pressure overload hypertrophy. Association with increased sarcoplasmic reticulum Ca2+-ATPase and alpha-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 alpha- and beta-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 (LVHcomp), whereas 6 had abnormal contraction, relaxation, and calcium handling (LVHdecomp). 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 LVHcomp and LVHdecomp. Myocytes from banded hearts treated with T4 were hypertrophied but had increased concentrations of alpha-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.
Chang
K C
KC
Department of Medicine, University of California, San Francisco, California 94143, USA.
Figueredo
V M
VM
Schreur
J H
JH
Kariya
K
K
Weiner
M W
MW
Simpson
P C
PC
Camacho
S A
SA
D000818:Animals; D001011:Aorta / Q000601:surgery; D001024:Aortic Valve Stenosis / Q000150:complications; D002118:Calcium / Q000378:metabolism*; D002135:Calcium-Binding Proteins / Q000378:metabolism; D000252:Calcium-Transporting ATPases / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D006352:Heart Ventricles / Q000166:cytology; D006973:Hypertension / Q000150:complications; D017379:Hypertrophy, Left Ventricular / Q000188:drug therapy* / Q000209:etiology; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects; D018995:Myosin Heavy Chains / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D012519:Sarcoplasmic Reticulum / Q000201:enzymology; D013974:Thyroxine / Q000627:therapeutic use*; D016277:Ventricular Function, Left / Q000187:drug effects*; D000099211:Phospholamban
D002118:Calcium; D002135:Calcium-Binding Proteins; D000252:Calcium-Transporting ATPases; D018995:Myosin Heavy Chains; D013974:Thyroxine; D000099211:Phospholamban