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


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.


Thyroid hormone Myocardial infarction Heart failure Cardiac regeneration Kinase signaling 



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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