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

Am J Physiol Endocrinol Metab. 2000 Dec;279(6):E1319-24. doi: 10.1152/ajpendo.2000.279.6.E1319.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Calcium-Transporting ATPases / genetics
  • Gene Expression / drug effects
  • Gene Expression / physiology
  • Hypertrophy, Left Ventricular / metabolism
  • Hypertrophy, Left Ventricular / physiopathology
  • Kv1.5 Potassium Channel
  • Male
  • Myocardial Infarction / metabolism*
  • Myocardial Infarction / physiopathology
  • Myocardial Ischemia / metabolism
  • Myocardial Ischemia / physiopathology
  • Myocardium / metabolism*
  • Myosin Heavy Chains / genetics*
  • Organ Size / drug effects
  • Organ Size / physiology
  • Potassium Channels / genetics
  • Potassium Channels, Voltage-Gated*
  • RNA, Messenger / analysis
  • Rats
  • Rats, Sprague-Dawley
  • Sarcoplasmic Reticulum Calcium-Transporting ATPases
  • Stroke Volume
  • Triiodothyronine / pharmacokinetics*


  • Atp2a2 protein, rat
  • Kcna5 protein, rat
  • Kv1.5 Potassium Channel
  • Potassium Channels
  • Potassium Channels, Voltage-Gated
  • RNA, Messenger
  • Triiodothyronine
  • Sarcoplasmic Reticulum Calcium-Transporting ATPases
  • Myosin Heavy Chains
  • Calcium-Transporting ATPases