人类衰竭心肌细胞中甲状腺激素受体和β-肾上腺素能受体表达降低。
Reduced expression of thyroid hormone receptors and beta-adrenergic receptors in human failing cardiomyocytes.
作者信息
Modesti Pietro Amedeo, Marchetta Matilde, Gamberi Tania, Lucchese Gianluca, Maccherini Massimo, Chiavarelli Mario, Modesti Alessandra
机构信息
Department of Critical Care Medicine, University of Florence, Viale Morgagni 85, 50134 Florence, Italy.
出版信息
Biochem Pharmacol. 2008 Feb 15;75(4):900-6. doi: 10.1016/j.bcp.2007.10.011. Epub 2007 Oct 16.
An altered thyroid hormone profile has been reported in patients with congestive heart failure. However, information regarding the status of thyroid hormone receptors in human failing cardiomyocytes is lacking. Therefore the expression of thyroid hormone and beta-adrenergic receptors was investigated in human ventricular cardiomyocytes isolated from patients with end-stage heart failure (FM, n=12), or from tentative donors (C, n=4). The expression of thyroid (TRalpha1, and TRbeta1) and beta-adrenergic receptors (ARB1 and ARB2) was measured at both the gene, and at the protein level. In FM the reduced mRNA expression of ARB1 (p<0.05, -37%) and ARB2 (p<0.05, -42%) was associated with a reduction of the messenger for TRalpha1 (p<0.05, -85%) and TRalpha2 (p<0.05, -73%). These findings were confirmed at the protein level for ARB1, ARB2 and TRalpha1. These data reveal that in human heart failure the reduction of beta-adrenergic receptors is associated with reduced expression of both TRalpha1 and TRalpha2 isoforms of thyroid hormone receptors.
据报道，充血性心力衰竭患者的甲状腺激素谱发生了改变。然而，关于人类衰竭心肌细胞中甲状腺激素受体状态的信息尚缺。因此，研究人员对从终末期心力衰竭患者（FM，n = 12）或潜在供体（C，n = 4）分离出的人类心室心肌细胞中甲状腺激素和β-肾上腺素能受体的表达进行了研究。在基因水平和蛋白质水平上测量了甲状腺（TRα1和TRβ1）和β-肾上腺素能受体（ARB1和ARB2）的表达。在FM组中，ARB1（p<0.05，-37%）和ARB2（p<0.05，-42%）的mRNA表达降低与TRα1（p<0.05，-85%）和TRα2（p<0.05，-73%）信使核糖核酸的减少有关。这些发现对于ARB1、ARB2和TRα1在蛋白质水平上得到了证实。这些数据表明，在人类心力衰竭中，β-肾上腺素能受体的减少与甲状腺激素受体的TRα1和TRα2亚型的表达降低有关。
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