Type II deiodinase and thyroid hormone receptor gene expression in the human heart

Thyroid hormone plays an important role on myocardial development and function. The effects of thyroid hormone are mediated by the receptor isoforms, ultimately regulating the expression of cardiac-specific genes. Local production of T3 and the physiological role of type II deiodination in the heart is still debated. 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 5'DII (dio2) and thyroid hormone receptors TRalpha1 and TRalpha2 among atrial and ventricular biopsies obtained from patients undergoing cardiac surgery. Twenty-nine patients (18 men and 11 women; age 63±13, mean±SD) were enrolled in the study and their thyroid hormone profiles determined. All the patients were euthyroid (TSH=1.7±1.3, FT3=2.3±0.7, FT4=15.1±2.7, mean±SD) and normotensive, 17 undergoing aorto-coronary bypass and 11 undergoing valve replacement (Left Ventricular Ejection Fraction=50.6±8.7; end-Diastolic Left Ventricle Diameter=50,2±5.7, mean±SD). Examination of total RNA extracted from atrium and ventricle biopsies, using conventional Reverse Transcriptase Polymerase Chain Reaction (RT-PCR) and subsequent semi-quantitative analysis, confirmed the expression of specific mRNAs encoding 5'DII (344 basepairs), TRalpha1 (325 basepairs) and TRalpha2 (259 basepairs). We found that the three studied genes dio2, TRalpha1 and TRalpha2 are expressed in the heart: dio2 measured 0.90 Arbitrary Units ± 0.66 (mean±SE) in the atrium and 1.56±0.66 in the ventricle; TRalpha1 measured 1.61±0.22 in the atrium and 2.0±0.38 in the ventricle; TRalpha2 measured 1.0±0.28 in the atrium. Significative correlations were found comparing 1) the semi-quantitative expression of TRalpha2 and the telediastolic diameter of the left ventricle (R=0.83, p=0.01) and 2) the semi-quantitative expression of TRalpha1 and FT3/FT4 ratio (R=0.60, p=0.05). Our data suggest that an alterate cardiac thyroidal pattern can be correlated with the progression of a low T3 state and a cardiac compromission, leading to an attenuation of thyroid hormone signaling during progression of heart dysfunction.