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Dose-dependent effects of thyroid hormone on post-ischemic cardiac performance: potential involvement of Akt and ERK signalings

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Abstract

The present study explored the effects of thyroid hormone (TH) treatment on post-ischemic cardiac function and potential implicated mechanisms. Acute myocardial infarction (AMI) was induced in mice by coronary artery ligation while sham-operated animals served as controls. This procedure resulted in a marked depression of cardiac function and significant reduction in TH levels in plasma. TH was given at a dose aiming to normalize T3 levels in plasma [AMI-TH (A)] and also at higher doses. The group of animals treated with the highest dose of TH, which displayed significantly increased mortality rate was included in the study [AMI-TH (B)]. In AMI-TH (A) mice, TH significantly improved left ventricular (LV) ejection fraction (EF%), [27.9% (1.4) in AMI versus 38.0 (3.1) in AMI-TH (A), P < 0.05], and favorably remodeled LV chamber while α-MHC was the dominant isoform expressed. In AMI-TH (B) mice, TH treatment resulted in increased mortality as compared to untreated mice (73% vs 47%, P < 0.05), while the favorable effect of TH was not evident in the survived animals. At the molecular level, TH, at the replacement dose, modestly increased p-Akt levels in the myocardium without any change in p-ERK levels. On the contrary, TH at the higher dose resulted in further increase in p-Akt along with an increase in p-ERK levels. In conclusion, TH appears to have a dose-dependent bimodal effect on post-ischemic cardiac performance and this effect may, at least in part, be mediated by a distinct pattern of activation of Akt and ERK signaling.

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Acknowledgment

The study was partly funded by ongoing European Community ITC-STREP FP7 PONTE Research Project (Project No. 247945).

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Authors and Affiliations

  1. Department of Pharmacology, University of Athens, 75 Mikras Asias Ave, 11527, Goudi, Athens, Greece

    Iordanis Mourouzis, Polixeni Mantzouratou, Georgios Galanopoulos, Erietta Kostakou, Nikolaos Roukounakis, Alexandros D. Kokkinos & Constantinos Pantos

  2. Biomedical Research Foundation, Academy of Athens, Athens, Greece

    Dennis V. Cokkinos

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  1. Iordanis Mourouzis
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  2. Polixeni Mantzouratou
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  3. Georgios Galanopoulos
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  8. Constantinos Pantos
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Correspondence to Constantinos Pantos.

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Mourouzis, I., Mantzouratou, P., Galanopoulos, G. et al. Dose-dependent effects of thyroid hormone on post-ischemic cardiac performance: potential involvement of Akt and ERK signalings. Mol Cell Biochem 363, 235–243 (2012). https://doi.org/10.1007/s11010-011-1175-9

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  • DOI: https://doi.org/10.1007/s11010-011-1175-9

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