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 TRa1 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; T 3 and T 4 levels in plasma were not changed at 2 weeks but T 3 was significantly lower and T 4 remained unchanged at 13 weeks. A twofold increase in TRa1 expression was observed after 13 weeks in the non-infarcted area, P!0.05 versus sham operated, while TRa1 expression remained unchanged at 2 weeks. A 2.2-fold decrease in TRb1 expression was found in the non-infarcted area at 13 weeks, P!0.05, while no change in TRb1 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 TRa1 and 1.6-fold decrease in TRb1 expression versus untreated, P!0.05. In conclusion, cardiac dysfunction which occurs at late stages after AMI is associated with increased expression of TRa1 receptor and lower circulating tri-iodothyronine levels. Thus, apo-TRa1 receptor state may prevail contributing to cardiac fetal phenotype. Furthermore, down-regulation of TRb1 also contributes to fetal phenotypic changes. a1-adrenergic signalling is, at least in part, involved in this response. 156 415-424 European Journal of Endocrinology

Thyroid hormone is a critical determinant of myocardial performance in patients with heart failure: potential therapeutic implications

“…However, it is now recognized that low total T 3 levels in plasma may be an independent factor for mortality in patients with heart failure (5,6), indicating that thyroid hormone probably has an important role in the pathophysiology of heart failure. Such a possibility is further supported by recent experimental studies which clearly demonstrate that changes in thyroid hormone-thyroid nuclear receptor axis occur in the failing myocardium and correlate to cardiac dysfunction (7)(8)(9)(10). Based on this evidence, the present study has further explored whether thyroid hormone can be correlated to functional myocardial status in patients with dilated cardiomyopathy of ischemic or non-ischemic origin.…”

“…There is accumulating experimental evidence showing that changes in thyroid hormone and/or thyroid hormone receptors (TRs) can occur in cardiac hypertrophy and myocardial infarction, and this seems to be of physiological relevance (7)(8)(9)(10). More importantly, after myocardial infarction in rats, changes in myosin isoform expression in the myocardium are evident, corresponding to exacerbation of cardiac dysfunction.…”

“…More importantly, after myocardial infarction in rats, changes in myosin isoform expression in the myocardium are evident, corresponding to exacerbation of cardiac dysfunction. This response is thought to be due to the TRa1 aporeceptor repressive activity (10). Interestingly, this type of TR appears to be overexpressed in human myocardium in patients with dilated cardiomyopathy (13).…”

‘Low — T3 syndrome’ among patients with acute myocardial infarction

“…This effect is modulated by TH reshaping LV chamber toward a more ellipsoidal shape. The above mentioned responses seem to involve distinct signaling pathways, comprising: low TH levels, increased D3 activity, increased expression of thyroid receptor protein α1 (TRα1) and decreased TR β1 protein expression in the myocardium [31,32].…”

The relationship of thyroid hormone status with myocardial function in stress cardiomyopathy

“…It has been demonstrated that the degree of thyroid dysfunction was associated with severity of diseases, and low levels of biologically active TH predicted poor prognosis in several diseases (26)(27)(28)(29)(30). Previous studies have reported that low total T 3 levels were associated with increased mortality and impaired cardiac function and were strong prognostic predictors of death in heart disease (31)(32)(33).…”