Thyroid hormone metabolism and cardiac gene expression after acute myocardial infarction in the rat
American Journal of Physiology. Endocrinology and Metabolism
Ojamaa, Kaie, Agnes Kenessey, Rajesh Shenoy, and Irwin Klein. Thyroid hormone metabolism and cardiac gene expression after acute myocardial infarction in the rat. Am J Physiol Endocrinol Metab 279: E1319-E1324, 2000.-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-Lthyronine (T 3 ), the cellular active hormone metabolite. T 3 has profound effects on the heart;
... ore, 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 Ͻ 0.001) decrease in percent ejection fraction (%EF) with a 32-35% increase (P Ͻ 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 ␣-myosin heavy chain (MHC), sarcoplasmic reticulum calcium-activated ATPase (SERCA2), and Kv1.5 mRNA, whereas ␤-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 ␤-MHC and Kv1.5 mRNA content was returned to control levels, ␣-MHC and SERCA2 were unresponsive to T 3 at replacement doses, and only at higher doses of T 3 was ␣-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.