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

被引:80
作者
Chang, KC
Figueredo, VM
Schreur, JHM
Kariya, K
Weiner, MW
Simpson, PC
Camacho, SA
机构
[1] UNIV CALIF SAN FRANCISCO, SAN FRANCISCO GEN HOSP, DIV CARDIOL, MED SERV CARDIOL, SAN FRANCISCO, CA 94110 USA
[2] UNIV CALIF SAN FRANCISCO, DEPT MED, SAN FRANCISCO, CA 94143 USA
[3] UNIV CALIF SAN FRANCISCO, DEPT RADIOL, SAN FRANCISCO, CA 94143 USA
[4] VET AFFAIRS MED CTR, RES SERV, SAN FRANCISCO, CA 94121 USA
关键词
contractility; myocardial relaxation; pathological hypertrophy; fluorescence; indo-1; AM;
D O I
10.1172/JCI119699
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
We asked whether thyroid hormone (T-4) 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 T-4 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 T-4 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 T-4 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 hormonelike signaling might be a therapeutic strategy for treating cardiac dysfunction in pathological hypertrophy and heart failure.
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页码:1742 / 1749
页数:8
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