Time-dependent changes in the expression of thyroid hormone receptor α1 in the myocardium after acute myocardial infarction: possible implications in cardiac remodelling

Abstract

The present study investigated whether changes in thyroid hormone (TH) signalling can occur after acute myocardial infarction (AMI) with possible physiological consequences on myocardial performance. TH may regulate several genes encoding important structural and regulatory proteins particularly through the TRα1 receptor which is predominant in the myocardium. AMI was induced in rats by ligating the left coronary artery while sham-operated animals served as controls. This resulted in impaired cardiac function in AMI animals after 2 and 13 weeks accompanied by a shift in myosin isoforms expression towards a fetal phenotype in the non-infarcted area. Cardiac hypertrophy was evident in AMI hearts after 13 weeks but not at 2 weeks. This response was associated with a differential pattern of TH changes at 2 and 13 weeks; T3 and T4 levels in plasma were not changed at 2 weeks but T3 was significantly lower and T4 remained unchanged at 13 weeks. A twofold increase in TRα1 expression was observed after 13 weeks in the non-infarcted area, P<0.05 versus sham operated, while TRα1 expression remained unchanged at 2 weeks. A 2.2-fold decrease in TRβ1 expression was found in the non-infarcted area at 13 weeks, P<0.05, while no change in TRβ1 expression was seen at 2 weeks. Parallel studies with neonatal cardiomyocytes showed that phenylephrine (PE) administration resulted in 4.5-fold increase in the expression of TRα1 and 1.6-fold decrease in TRβ1 expression versus untreated, P<0.05. In conclusion, cardiac dysfunction which occurs at late stages after AMI is associated with increased expression of TRα1 receptor and lower circulating tri-iodothyronine levels. Thus, apo-TRα1 receptor state may prevail contributing to cardiac fetal phenotype. Furthermore, down-regulation of TRβ1 also contributes to fetal phenotypic changes. α1-adrenergic signalling is, at least in part, involved in this response.