Thyroid hormone metabolism and cardiac gene expression after acute myocardial infarction in the rat
Thyroid hormone metabolism and cardiac gene expression after acute myocardial infarction in the rat
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DOI：
10.1152/ajpendo.2000.279.6.e1319
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发表时间：
2000-12-01
影响因子：
5.1
通讯作者：
Klein, I
中科院分区：
文献类型：
--
作者：
Ojamaa, K;Kenessey, A;Klein, I
在由冠状动脉结扎产生的急性心肌梗塞 (MI) 大鼠模型中，甲状腺激素代谢发生改变，血清三碘-L-甲状腺氨酸 (T-3)（细胞活性激素代谢物）显着降低 (54%)。 T-3对心脏有深远的影响；因此，大鼠在急性心肌梗死后接受 T-3 治疗 2 或 3 周，无论是替代剂量还是提高剂量，以确定心脏功能和基因表达是否可以正常化。急性心肌梗死导致射血分数百分比 (% EF) 降低 50% (P < 0.001)，而代偿性左心室 (LV) 肥大增加 32-35% (P < 0.01)。用替代剂量或增加剂量的 T-3 治疗 MI 动物后，%EF 分别显着增加至对照的 64% 和 73%。 MI后肥大的左心室中多个T-3反应基因的表达水平发生改变，包括α-肌球蛋白重链（MHC）、肌浆网钙激活ATP酶（SERCA2）和Kv1.5 mRNA显着减少，而β-MHC和受磷蛋白（PLB）mRNA显着增加。血清 T-3 正常化并没有恢复所有 T-3 调节基因的表达，表明梗死后心肌中 T-3 反应性发生改变。虽然β-MHC和Kv1.5 mRNA含量恢复到对照水平，但α-MHC和SERCA2在替代剂量下对T-3没有反应，并且仅在较高剂量的T-3下α-MHC mRNA才恢复到对照值。本研究表明，大鼠急性心肌梗死与血清 T-3 水平下降、左心室功能障碍和 T-3 反应基因表达改变有关，T-3 治疗显着改善心脏功能，部分但不是全部基因表达变化正常化。
In a rat model of acute myocardial infarction (MI) produced by coronary artery ligation, thyroid hormone metabolism was altered with significant reductions (54%) in serum triiodo-L-thyronine (T-3), the cellular active hormone metabolite. T-3 has profound effects on the heart; therefore, rats were treated with T-3 after acute MI for 2 or 3 wk, at either replacement or elevated doses, to determine whether cardiac function and gene expression could be normalized. Acute MI resulted in a 50% (P < 0.001) decrease in percent ejection fraction (% EF) with a 32-35% increase (P < 0.01) in compensatory left ventricle (LV) hypertrophy. Treatment of the MI animals with either replacement or elevated doses of T-3 significantly increased %EF to 64 and 73% of control, respectively. Expression levels of several T-3-responsive genes were altered in the hypertrophied LV after MI, including significant decreases in alpha -myosin heavy chain (MHC), sarcoplasmic reticulum calcium-activated ATPase (SERCA2), and Kv1.5 mRNA, whereas beta -MHC and phospholamban (PLB) mRNA were significantly increased. Normalization of serum T-3 did not restore expression of all T-3-regulated genes, indicating altered T-3 responsiveness in the postinfarcted myocardium. Although beta -MHC and Kv1.5 mRNA content was returned to control levels, alpha -MHC and SERCA2 were unresponsive to T-3 at replacement doses, and only at higher doses of T-3 was alpha -MHC mRNA returned to control values. The present study showed that acute MI in the rat was associated with a fall in serum T-3 levels, LV dysfunction, and altered expression of T-3-responsive genes and that T-3 treatment significantly improved cardiac function, with normalization of some, but not all, of the changes in gene expression.