Thyroid hormone receptor and IGF1/IGFR systems: possible relations in the human heart.
Thyroid hormone (TH) and insulin growth factor 1 (IGF1) systems both play crucial roles in the regulation of cardiac remodeling and hypertrophy processes. The mediation of this regulation is attributed to specific thyroid hormone receptors (TRs) and to the IGF1 receptor (IGF1R). In humans, 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 and IGF1 signaling in human myocardium through the evaluation of the gene expression of TRalpha1, TRalpha2, TRbeta1 and IGF1R among atrial and ventricular biopsies obtained from patients undergoing cardiac surgery. Moreover, we evaluated possible correlations between TR and IGF1/IGF1R systems. Eighteen clinically and biochemically euthyroid patients (aged 68.3+/-3.2years, mean+/-SEM) without overt heart failure (Ejection Fraction (EF), 46.4+/-2.8%; Left Ventricular End Diastolic Diameter (LVEDD), 54.3+/-1.2mm, mean+/-SEM; NYHA I-II) were enrolled in the study: 13 undergoing aorto-coronary bypass and 5 undergoing valve replacement (aortic/mitral valve). The examination of total RNA, using real time PCR (LightCycler Technology) confirmed the expression of specific mRNAs encoding TRalpha1, TRalpha2, TRbeta1 and both IGF1 and IGF1R. We found that the three TR genes are co-expressed in the human atrium and ventricle. The finding of a strong correlation among IGF1R and the three TR genes expressed in the atrium (p<0.001) and among the three TRs in the atrium (p<0.001) suggests the interesting possibility that the two systems, TRs and IGF1R could also be functionally associated.
Sabatino
Laura
L
Clinical Physiology Institute, National Council Research, Via Moruzzi 1, 56124 Pisa, Italy. lauretta@ifc.cnr.it
Gliozheni
Enri
E
Molinaro
Sabrina
S
Bonotti
Alessandra
A
Azzolina
Sienne
S
Popoff
Georges
G
Carpi
Angelo
A
Iervasi
Giorgio
G
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001026:Coronary Artery Bypass; D005163:Factor Analysis, Statistical; D005260:Female; D015870:Gene Expression; D006325:Heart Atria / Q000378:metabolism; D006331:Heart Diseases / Q000175:diagnosis / Q000378:metabolism / Q000601:surgery; D006351:Heart Valves / Q000601:surgery; D006352:Heart Ventricles / Q000378:metabolism; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000096:biosynthesis* / Q000235:genetics; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000378:metabolism*; D011336:Probability; D020033:Protein Isoforms / Q000096:biosynthesis / Q000235:genetics; D017526:Receptor, IGF Type 1 / Q000096:biosynthesis* / Q000235:genetics; D015398:Signal Transduction; D037021:Thyroid Hormone Receptors alpha / Q000096:biosynthesis* / Q000235:genetics; D037042:Thyroid Hormone Receptors beta / Q000096:biosynthesis* / Q000235:genetics; D018487:Ventricular Dysfunction, Left / Q000175:diagnosis
D020033:Protein Isoforms; D037021:Thyroid Hormone Receptors alpha; D037042:Thyroid Hormone Receptors beta; D007334:Insulin-Like Growth Factor I; D017526:Receptor, IGF Type 1