title: 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 (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.
authors.affiliation: Divisions of Endocrinology and Pediatric Cardiology, Departments of Medicine and Pediatrics, North Shore University Hospital/New York University School of Medicine, Manhasset, New York 11030, USA. kojamaa@nshs.edu
authors.forename: K
authors.initials: K
authors.lastname: Ojamaa
authors.forename: A
authors.initials: A
authors.lastname: Kenessey
authors.forename: R
authors.initials: R
authors.lastname: Shenoy
authors.forename: I
authors.initials: I
authors.lastname: Klein
mesh_terms: D000818:Animals; D000252:Calcium-Transporting ATPases / Q000235:genetics; D015870:Gene Expression / Q000187:drug effects / Q000502:physiology; D017379:Hypertrophy, Left Ventricular / Q000378:metabolism / Q000503:physiopathology; D051666:Kv1.5 Potassium Channel; D008297:Male; D009203:Myocardial Infarction / Q000378:metabolism* / Q000503:physiopathology; D017202:Myocardial Ischemia / Q000378:metabolism / Q000503:physiopathology; D009206:Myocardium / Q000378:metabolism*; D018995:Myosin Heavy Chains / Q000235:genetics*; D009929:Organ Size / Q000187:drug effects / Q000502:physiology; D015221:Potassium Channels / Q000235:genetics; D024642:Potassium Channels, Voltage-Gated; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D013318:Stroke Volume; D014284:Triiodothyronine / Q000493:pharmacokinetics*
chemical_list: C506948:Atp2a2 protein, rat; C496983:Kcna5 protein, rat; D051666:Kv1.5 Potassium Channel; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D012333:RNA, Messenger; D014284:Triiodothyronine; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D018995:Myosin Heavy Chains; D000252:Calcium-Transporting ATPases