Thyroid hormone receptor alpha1, alpha2 and beta1 gene expression in the human heart

Nuclear thyroid hormone receptors (TRs) play a fundamental role in mediating the effects of thyroid hormone (TH) in the heart. Two TR genes are expressed in the heart, TRalpha and TRbeta. Each gene generates two isoforms: TRalpha1, TRalpha2 and TRbeta1, TRbeta2. The aim of the present work was to study the local thyroid hormone signaling in human myocardium through the evaluation of the gene expression of TRs TRalpha1, TRalpha2 and TRbeta1 among atrial and ventricular biopsies obtained from patients undergoing cardiac surgery. Ten clinically and biochemically euthyroid patients (age 68.5?13.6 mean?SD) without overt heart failure (LV-EF=45?10.3; end-Diastolic LV-Diameter=55.4?1.7, mean±SD; NYHA I-II) were enrolled in the study: 6 undergoing aorto-coronary bypass and 4 undergoing valve replacement (aorta/mitral valve). Examination of total RNA, using Real time PCR (Light Cycler Technology) confirmed the expression of specific mRNAs encoding TRalpha1, TRalpha2 and TRbeta1. We found that the three genes are expressed both in the atrium (Bypass: TRalpha1 0.59?0.19, TRalpha2 0.58?0.21, TRbeta1 0.75?0.16; Valvular: TRalpha1 0.84?1.04, TRalpha2 0.85?0.88, TRbeta1 0.69?0.58; mean?SD), and in the ventricle (Bypass: TRalpha1 1.28?0.53, TRalpha2 1.21?0.21, TRbeta1 1.23?0.65; Valvular: TRalpha1 2.39?2.18, TRalpha2 1.69?1.40, TRbeta1 1.34?0.76; mean?SD) and that in bypass patients TR expression is significantly higher in ventricle than in atrium (TRalpha1 p<0.04; TRalpha2 p<0.002). A linear regression was found between TRalpha1 and TRalpha2 (R = 0.89, p<0.001), TRalpha1 and TRbeta1 (R = 0.85, p<0.001) and TRalpha2 and TRbeta1 (R = 0.78, p<0.01). Our data, taken as a whole, suggest that changes in the TR cardiac expression might be associated to the evolution of heart disease and it represents a main target for possible therapeutic approaches.