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Thyroid hormone receptors α1 and β1 are downregulated in the post-infarcted rat heart: consequences on the response to ischaemia-reperfusion

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Abstract

There is accumulating evidence that thyroid hormone metabolism is altered after myocardial infarction (AMI) but its physiological relevance remains largely unknown. The present study investigated the possible role of thyroid hormone signaling in the response of the post-infarcted heart to ischaemia-reperfusion. Wistar rats were subjected to left coronary artery ligation (AMI), or sham operation (SHAM). After 8 weeks, hearts from AMI and SHAM rats were perfused in Langendorff mode and subjected to 20 min of zero-flow global ischaemia (I) and 45 min of reperfusion (R); AMI(I/R), n = 7 and SHAM(I/R), n = 7. Basal left ventricular pressure (LVDP), +dp/dt, and –dp/dt were significantly reduced. Left ventricular weight of the viable myocardium was increased by 14% in the AMI as compared to SHAM hearts, P < 0.05. T3 and T4 plasma levels in nM were 1.83 (0.08) and 53.3 (2.9) for SHAM and 1.76 (0.06) and 59.4 (5.2) for AMI rats, respectively, P > 0.05. TRα1 and TRβ1 expression levels were 1.3- and 1.8-fold less in AMI than in SHAM hearts, P < 0.05. Furthermore, SERCA and NHE1 expression levels were 2.1- and 1.8-fold less in AMI than in SHAM, P < 0.05. PKCε was 1.35-fold more in AMI compared to SHAM, P < 0.05. Myocardial glycogen content (in µmol/g) was 7.8 (1.2) in AMI as compared to 4.4 (0.5) for SHAM hearts, P < 0.05. After I/R, left ventricular end-diastolic pressure at 45 min of R (LVEDP45 in mmHg) was 20.3 (3.2) for AMI(I/R) vs 50.6 (4.8) mmHg for SHAM(I/R), P < 0.05. LDH release per gram of tissue was 251 (103) for AMI(I/R) and 762 (74) for SHAM(I/R), P < 0.05. In conclusion, TRα1 and TRβ1 are downregulated after myocardial infarction and this was associated with altered expression of thyroid hormone responsive genes and increased tolerance of the post-infarcted heart to ischaemia-reperfusion injury.

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Authors and Affiliations

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

    C. Pantos, I. Mourouzis, T. Saranteas, I. Paizis, C. Xinaris & V. Malliopoulou

  2. 1st Cardiology Department, Onassis Cardiac Surgery Center, 356 Sygrou Ave. , 17674, Kallithea, Athens, Greece

    D. V. Cokkinos

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  1. C. Pantos
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  2. I. Mourouzis
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  5. C. Xinaris
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Pantos, C., Mourouzis, I., Saranteas, T. et al. Thyroid hormone receptors α1 and β1 are downregulated in the post-infarcted rat heart: consequences on the response to ischaemia-reperfusion. Basic Res Cardiol 100, 422–432 (2005). https://doi.org/10.1007/s00395-005-0545-4

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  • DOI: https://doi.org/10.1007/s00395-005-0545-4

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