Rebuilding the post-infarcted myocardium by activating ‘physiologic’ hypertrophic signaling pathways: the thyroid hormone paradigm Constantinos Pantos Æ Iordanis Mourouzis Æ Dennis V. Cokkinos Published online: 5 September 2008 Ó Springer Science+Business Media, LLC 2008 Abstract Viable myocardium undergoes several changes in the course of cardiac remodeling following myocardial infarction aiming to adapt the heart to the hemodynamic compromise. This response is characterized by reactivation of the fetal transcriptional program and results in cardiac dysfunction. Changes in thyroid hormone (TH)-TH recep- tors (TRs) axis occur in the course of post-infarction cardiac remodeling and seem to contribute to cardiac fetal phenotype. TH can ‘‘rebuild’’ the post-infarcted heart by preventing the fetal-like pattern of contractile proteins expression, normalizing wall tension, and optimizing car- diac chamber geometry. This effect seems to be attributed to TH pleiotropic cellular actions; TH promotes tissue growth and differentiation and favorably remodels cardiac cell while increases cellular survival upon stress. TH may constitute a new therapeutic option for mending the ischemic myocardium. Keywords Cardiac remodeling Á Myocardial infarction Á Heart failure Á Hypertrophy Á Thyroid hormone Á Thyroid hormone receptors Á Apoptosis Á Inotropes Á MAP kinases Á Heat shock proteins Introduction Reduced cardiac function progressively occurs after acute myocardial infarction due to changes in the viable non- ischemic myocardium, a process known as cardiac remod- eling. This response is characterized by the development of cardiac hypertrophy, altered cardiac chamber geometry, shift of contractile proteins’ expression to fetal pattern, switch to glucose metabolism, and the induction of fibrosis [1, 2]. The mechanisms underlying this process are not fully understood. However, it has recently been recognized that hormones implicated at early developmental stages, such as thyroid hormone (TH) may have a role in the process of cardiac remodeling. In fact, changes in TH-TH receptors (TRs) axis occur in the course of post-infarction cardiac remodeling and seem to contribute to fetal transcriptional programing of ‘pathological hypertrophy’ [3]. Furthermore, TH seems to have the ability to ‘‘rebuild’’ the post-infarcted heart by preventing the fetal-like pattern of contractile proteins expression, normalizing wall tension and optimiz- ing cardiac chamber geometry. This effect may be attributed to pleiotropic TH cellular actions; TH is critical in tissue growth and differentiation and as such TH regulates metabolism, contractile and electrical function, response to stress and optimizes cellular morphology. Based on this evidence, TH appears to constitute a paradigm of an effective therapeutic strategy for rebuilding the ‘‘broken heart’’. TH signaling in post-ischemic cardiac remodeling: a ‘‘player’’ or ‘‘bystander’’ Several changes in TH–TRs axis have been identified in the course of cardiac remodeling after myocardial infarction C. Pantos (&) Á I. Mourouzis Department of Pharmacology, University of Athens, School of Medicine, 75 Mikras Asias Avenue, 11527 Goudi, Athens, Greece e-mail: cpantos@cc.uoa.gr D. V. Cokkinos 1st Cardiology Department, Onassis Cardiac Surgery Center, Athens, Greece 123 Heart Fail Rev (2010) 15:143–154 DOI 10.1007/s10741-008-9111-0