Sabatino Laura, Gliozheni Enri, Molinaro Sabrina, Bonotti Alessandra, Azzolina Sienne, Popoff Georges, Carpi Angelo, Iervasi Giorgio
Clinical Physiology Institute, National Council Research, Via Moruzzi 1, 56124 Pisa, Italy.
Biomed Pharmacother. 2007 Sep;61(8):457-62. doi: 10.1016/j.biopha.2007.04.002. Epub 2007 May 22.
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.
甲状腺激素（TH）和胰岛素生长因子1（IGF1）系统在心脏重塑和肥大过程的调节中均发挥着关键作用。这种调节作用通过特定的甲状腺激素受体（TRs）和IGF1受体（IGF1R）介导。在人类中，心脏表达两种TR基因，即TRα和TRβ。每个基因产生两种异构体：TRα1、TRα2和TRβ1、TRβ2。本研究的目的是通过评估心脏手术患者心房和心室活检组织中TRα1、TRα2、TRβ1和IGF1R的基因表达，来研究人类心肌中的局部甲状腺激素和IGF1信号传导。此外，我们评估了TR与IGF1/IGF1R系统之间可能存在的相关性。18例临床和生化指标正常甲状腺功能（年龄68.3±3.2岁，平均值±标准误）且无明显心力衰竭（射血分数（EF）为46.4±2.8%；左心室舒张末期内径（LVEDD）为54.3±1.2mm，平均值±标准误；纽约心脏协会心功能分级I-II级）的患者纳入研究：13例行主动脉冠状动脉搭桥术，5例行瓣膜置换术（主动脉/二尖瓣）。使用实时PCR（LightCycler技术）检测总RNA，证实了编码TRα1、TRα2、TRβ1以及IGF1和IGF1R的特定mRNA的表达。我们发现这三种TR基因在人类心房和心室中共同表达。在心房中IGF1R与三种TR基因之间存在强相关性（p<0.001）以及三种TR之间存在强相关性（p<0.001），这一发现提示了TRs和IGF1R这两个系统可能在功能上也存在关联的有趣可能性。
