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Molecular and Cellular Biochemistry

, Volume 363, Issue 1–2, pp 235–243 | Cite as

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

  • Iordanis Mourouzis
  • Polixeni Mantzouratou
  • Georgios Galanopoulos
  • Erietta Kostakou
  • Nikolaos Roukounakis
  • Alexandros D. Kokkinos
  • Dennis V. Cokkinos
  • Constantinos Pantos
Article

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.

Keywords

Thyroid hormone Myocardial infarction Heart failure Cardiac regeneration Kinase signaling 

Notes

Acknowledgment

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

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Copyright information

© Springer Science+Business Media, LLC. 2011

Authors and Affiliations

  • Iordanis Mourouzis
    • 1
  • Polixeni Mantzouratou
    • 1
  • Georgios Galanopoulos
    • 1
  • Erietta Kostakou
    • 1
  • Nikolaos Roukounakis
    • 1
  • Alexandros D. Kokkinos
    • 1
  • Dennis V. Cokkinos
    • 2
  • Constantinos Pantos
    • 1
  1. 1.Department of PharmacologyUniversity of AthensGoudi, AthensGreece
  2. 2.Biomedical Research FoundationAcademy of AthensAthensGreece

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