Thyroid hormone metabolism and cardiac gene expression after acute myocardial infarction in the rat

Abstract

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 (T3), the cellular active hormone metabolite. T3 has profound effects on the heart; therefore, rats were treated with T3 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 T3 significantly increased %EF to 64 and 73% of control, respectively. Expression levels of several T3-responsive genes were altered in the hypertrophied LV after MI, including significant decreases in α-myosin heavy chain (MHC), sarcoplasmic reticulum calcium-activated ATPase (SERCA2), and Kv1.5 mRNA, whereas β-MHC and phospholamban (PLB) mRNA were significantly increased. Normalization of serum T3 did not restore expression of all T3-regulated genes, indicating altered T3 responsiveness in the postinfarcted myocardium. Although β-MHC and Kv1.5 mRNA content was returned to control levels, α-MHC and SERCA2 were unresponsive to T3 at replacement doses, and only at higher doses of T3 was α-MHC mRNA returned to control values. The present study showed that acute MI in the rat was associated with a fall in serum T3 levels, LV dysfunction, and altered expression of T3-responsive genes and that T3 treatment significantly improved cardiac function, with normalization of some, but not all, of the changes in gene expression.