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Thyroid hormone receptor alpha1: a switch to cardiac cell 'metamorphosis'?

100%

Pantos C., Xinaris C., Mourouzis I., Perimenis P., Politi E., Spanou D., Cokkinos D. V.

Journal of Physiology and Pharmacology

2008

tom 59

nr 2

Thyroid hormone receptor alphalpha1 (TRalpha1) is predominantly expressed in the myocardium but its biological function under physiological or pathological conditions remains largely unknown. The present study investigated possible interactions between alpha1 adrenergic and thyroid hormone signaling at the level of TRalpha1, potential underlying mechanisms and physiological consequences, as well as the role of TRalpha1 in cell differentiation. This may be of physiological relevance since both thyroid hormone and adrenergic signalling are implicated in the pathophysiology of cardiac remodelling. Neonatal cardiomyocytes obtained from newborn rats (2-3 days) were exposed to phenylephrine (PE, an alpha1 adrenergic agonist) for 5 days, in the absence or excess of T3 in the culture medium. PE, in the absence of T3, resulted in 5.0 fold increase in TRalpha1 expression in nucleus and 2.0 fold decrease in TRalpha1 expression in cytosol, P<0.05. As a result, a fetal pattern of myosin isoform expression with marked expression of ß–MHC was observed in PE treated vs the untreated cells, P<0.05. PD98059 (an ERK signalling inhibitor) abrogated this response. In the presence of T3 in the culture medium, TRalpha1 expression was increased 1.6 fold in nucleus and 2.0 fold in cytosol in PE-T3 vs PE treated cells, P<0.05, and the fetal pattern of myosin isoform expression was prevented. Parallel studies with H9c2 myoblasts showed that reduction of T3 binding to TRalpha1 receptor delayed cardiac myoblasts differentiation without affecting proliferation. In conclusion, in neonatal cardiomyocytes, nuclear TRalpha1 is overexpressed after prolonged activation of the alpha1- adrenergic signalling by PE. This response seems to be an ERK kinase dependent process. Over-expression of TRalpha1 may lead to fetal cardiac phenotype in the absence of thyroid hormone availability. Furthermore, TRalpha1 seems to be critical in cardiac myoblast differentiation.

Thyroid hormone at supra-physiological dose optimizes cardiac geometry and improves cardiac function in rats with old myocardial infarction

84%

Pantos C., Mourouzis I., Tsagoulis N., Markakis K., Galanopoulos G., Roukounakis N., Perimenis P., Liappas A., Cokkinos D. V.

Journal of Physiology and Pharmacology

2009

tom 60

nr 3

49-56

Thyroid hormone (TH) is critical in cardiac cell differentiation (regulating contractile proteins and cell geometry) and this effect could be potentially exploited therapeutically in reversing the process of de-differentiation which underlies postischemic cardiac remodeling. Acute myocardial infarction was induced in male Wistar rats by ligating left coronary artery (AMI, n=8), while sham operated animals served as control (SHAM, n=8). 13 weeks after AMI, TH was administered in a group of animals for 4 weeks (AMI-THYR, n=9). TH significantly increased ß-MHC and decreased -MHC expression in the myocardium. This response was accompanied by changes in cardiac geometry: sphericity index, (SI, long to short axis ratio) was found to be 1.95 (SEM, 0.02) in SHAM, 1.51(0.03) in AMI and 1.64(0.03) in AMI-THYR, p<0.05. As a consequence, cardiac function was significantly improved: left ventricular ejection fraction (EF%) was 74.5% (SEM, 2.8) in SHAM vs 29.5% (2.1) in AMI, and 40.0% in AMI-THYR, p<0.05. Furthermore, +dp/dt and -dp/dt were 4250 (127) and 2278 (55) in SHAM vs 2737(233) and 1508 (95) in AMI vs 3866 (310) and 2137(111) in AMI -THYR, respectively, p<0.05. TH treatment partially reverses cardiac dysfunction in rats with old myocardial infarction by favorably changing cardiac chamber geometry and expression of myosin isoforms. Thyroid hormone, unlike current treatments, appears to be a paradigm of therapeutic intervention which aims at restoring cardiac geometry and may prove new effective treatment for heart failure.

Ograniczanie wyników

2 Journal of Physiology and Pharmacology

2 Cokkinos D. V.

2 Mourouzis I.

2 Pantos C.

2 Perimenis P.

1 Galanopoulos G.

1 Liappas A.

1 Markakis K.

1 Politi E.

1 Roukounakis N.

1 Spanou D.

1 Tsagoulis N.

1 Xinaris C.

1 2009

1 2008

Wyniki wyszukiwania

Thyroid hormone receptor alpha1: a switch to cardiac cell 'metamorphosis'?

Thyroid hormone at supra-physiological dose optimizes cardiac geometry and improves cardiac function in rats with old myocardial infarction