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Thyroid hormone can favorably remodel the diabetic myocardium after acute myocardial infarction

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Abstract

It has been previously shown that regulators of physiological growth such as thyroid hormone (TH) can favorably remodel the post ischaemic myocardium. Here, we further explored whether this effect can be preserved in the presence of co-morbidities such as diabetes which accelerates cardiac remodeling and increases mortality after myocardial infarction. Acute myocardial infarction (AMI) was induced by left coronary ligation in rats with type I diabetes (DM) induced by streptozotocin administration (STZ; 35 mg/kg; i.p.) while sham-operated animals served as controls (SHAM). AMI resulted in distinct changes in cardiac function and geometry; EF% was significantly decreased in DM-AMI [37.9 ± 2.0 vs. 74.5 ± 2.1 in DM-SHAM]. Systolic and diastolic chamber dimensions were increased without concomitant increase in wall thickness and thus, wall tension index [WTI, the ratio of (Left Ventricular Internal Diameter at diastole)/2*(Posterior Wall thickness)], an index of wall stress, was found to be significantly increased in DM-AMI; 2.27 ± 0.08 versus 1.70 ± 0.05. 2D-Strain echocardiographic analysis showed reduced systolic radial strain in all segments, indicating increased loss of cardiac myocytes in the infarct related area and less compensatory hypertrophy in the viable segments. This response was accompanied by a marked decrease in the expression of TRα1 and TRβ1 receptors in the diabetic myocardium without changes in circulating T3 and T4. Accordingly, the expression of TH target genes related to cardiac contractility was altered; β-MHC and PKCα were significantly increased. TH (L-T4 and L-T3) administration prevented these changes and resulted in increased EF%, normal wall stress and increased systolic radial strain in all myocardial segments. Acute myocardial infarction in diabetic rats results in TH receptor down-regulation with important physiological consequences. TH treatment prevents this response and improves cardiac hemodynamics.

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Acknowledgments

S. Niarchos foundation and the Hellenic Cardiology Society for supporting this piece of work.

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Authors and Affiliations

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

    Christos Kalofoutis, Iordanis Mourouzis, Georgios Galanopoulos, Antonios Dimopoulos, Philippos Perimenis, Danai Spanou & Constantinos Pantos

  2. Onassis Cardiac Surgery Center, 356 Sygrou Ave, 17674, Kallithea, Athens, Greece

    Dennis V. Cokkinos

  3. Biomedical Research Foundation, Academy of Athens, 4 Soranou Ephessiou, 115 27 , Athens, Greece

    Dennis V. Cokkinos

  4. School of Forensic and Investigative Science, University of Central Lancashire, Preston, Lancashire, UK

    Christos Kalofoutis & Jaipaul Singh

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  1. Christos Kalofoutis
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  2. Iordanis Mourouzis
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  9. Constantinos Pantos
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Correspondence to Constantinos Pantos.

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Kalofoutis, C., Mourouzis, I., Galanopoulos, G. et al. Thyroid hormone can favorably remodel the diabetic myocardium after acute myocardial infarction. Mol Cell Biochem 345, 161–169 (2010). https://doi.org/10.1007/s11010-010-0569-4

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  • DOI: https://doi.org/10.1007/s11010-010-0569-4

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