Molecular and Cellular Biochemistry

, Volume 379, Issue 1–2, pp 97–105 | Cite as

Inhibition of thyroid hormone receptor α1 impairs post-ischemic cardiac performance after myocardial infarction in mice

  • Iordanis Mourouzis
  • Erietta Kostakou
  • Georgios Galanopoulos
  • Polixeni Mantzouratou
  • Constantinos Pantos


Thyroid hormone receptor α1 (TRα1) is shown to be critical for the maturation of cardiomyocytes and for the cellular response to stress. TRα1 is altered during post ischemic cardiac remodeling but the physiological significance of this response is not fully understood. Thus, the present study explored the potential consequences of selective pharmacological inhibition of TRα1 on the mechanical performance of the post-infarcted heart. Acute myocardial infarction was induced in mice (AMI), while sham operated animals served as controls (SHAM). A group of mice was treated with debutyl-dronedarone (DBD), a selective TRα1 inhibitor (AMI–DBD). AMI resulted in low T3 levels in plasma and in down-regulation of TRα1 and TRβ1 expression. Left ventricular ejection fraction (LVEF%) was significantly reduced in AMI [33 (SEM 2.1) vs 79(2.5) in SHAM, p < 0.05] and was further declined in AMI–DBD [22(1.1) vs 33(2.1), respectively, p < 0.05]. Cardiac mass was increased in AMI but not in AMI–DBD hearts, resulting in significant increase in wall tension index. This increase in wall stress was accompanied by marked activation of p38 MAPK, a kinase that is sensitive to mechanical stretch and exerts negative inotropic effect. Furthermore, AMI resulted in β-myosin heavy chain overexpression and reduction in the ratio of SR(Ca)ATPase to phospholamban (PLB). The latter further declined in AMI–DBD mainly due to increased expression of PLB. AMI induces downregulation of thyroid hormone signaling and pharmacological inhibition of TRα1 further depresses post-ischemic cardiac function. p38 MAPK and PLB may, at least in part, be involved in this response.


Thyroid hormone TRα1 receptor Myocardial infarction Heart failure Kinase signaling 



This study was supported by Alexander S. Onassis Foundation and M. Zobanakis.

Conflict of Interest

None declared.


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Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Iordanis Mourouzis
    • 1
  • Erietta Kostakou
    • 1
  • Georgios Galanopoulos
    • 1
  • Polixeni Mantzouratou
    • 1
  • Constantinos Pantos
    • 1
  1. 1.Department of PharmacologyUniversity of AthensGoudi, AthensGreece

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