Thyroid hormone can favorably remodel the diabetic myocardium after acute myocardial infarction Christos Kalofoutis • Iordanis Mourouzis • Georgios Galanopoulos • Antonios Dimopoulos • Philippos Perimenis • Danai Spanou • Dennis V. Cokkinos • Jaipaul Singh • Constantinos Pantos Received: 3 May 2010 / Accepted: 29 July 2010 / Published online: 22 August 2010 Ó Springer Science+Business Media, LLC. 2010 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 thick- ness 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 signif- icantly 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 TRa1 and TRb1 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; b-MHC and PKCa 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 dia- betic rats results in TH receptor down-regulation with important physiological consequences. TH treatment pre- vents this response and improves cardiac hemodynamics. Keywords Diabetes Á Myocardial infarction Á Thyroid hormone receptors Á Heart failure Á Myocardial ischemia Á Cardiac remodeling Introduction Acute myocardial infarction results in cardiac dysfunction due to myocardial loss and a series of changes in the non- ischaemic myocardium which include changes in the chamber size and shape and the interstitial structure, a process collectively known as cardiac remodeling. One main feature of cardiac remodeling is the recapitulation of fetal gene reprogramming leading to cell de-differentiation [1]. The underlying mechanisms of this response are not fully understood. However, it is now recognized that hor- mone signaling related to cell differentiation, such as thy- roid hormone (TH), may be of physiological relevance in C. Kalofoutis Á I. Mourouzis Á G. Galanopoulos Á A. Dimopoulos Á P. Perimenis Á D. Spanou Á C. Pantos (&) Department of Pharmacology, University of Athens, 75 Mikras Asias Ave, 11527 Goudi, Athens, Greece e-mail: cpantos@med.uoa.gr D. V. Cokkinos Onassis Cardiac Surgery Center, 356 Sygrou Ave, 17674 Kallithea, Athens, Greece D. V. Cokkinos Biomedical Research Foundation, Academy of Athens, 4 Soranou Ephessiou, 115 27 Athens, Greece C. Kalofoutis Á J. Singh School of Forensic and Investigative Science, University of Central Lancashire, Preston, Lancashire, UK 123 Mol Cell Biochem (2010) 345:161–169 DOI 10.1007/s11010-010-0569-4