title: Cardiomyocyte-specific inactivation of thyroid hormone in pathologic ventricular hypertrophy: an adaptative response or part of the problem?
abstract: Recent studies in various rodent models of pathologic ventricular hypertrophy report the re-expression of deiodinase type 3 (D3) in cardiomyocytes. D3 inactivates thyroid hormone (T3) and is mainly expressed in tissues during development. The stimulation of D3 activity in ventricular hypertrophy and subsequent heart failure is associated with severe impairment of cardiac T3 signaling. Hypoxia-induced signaling appears to drive D3 expression in the hypertrophic cardiomyocyte, but other signaling cascades implicated in hypertrophy are also capable of stimulating transcription of the DIO3 gene. Many cardiac genes are transcriptionally regulated by T3 and impairment of T3 signaling will not only reduce energy turnover, but also lead to changes in gene expression that contribute to contractile dysfunction in pathologic remodeling. Whether stimulation of D3 activity and the ensuing local T3-deficiency is an adaptive response of the stressed heart or part of the pathologic signaling network leading to heart failure, remains to be established.
authors.affiliation: Department of Physiology, Institute for Cardiovascular Research, VU University Medical Center Amsterdam, Van der Boechorststraat 7, Amsterdam, 1081 BT, The Netherlands.
authors.forename: Christine J
authors.initials: CJ
authors.lastname: Pol
authors.forename: Alice
authors.initials: A
authors.lastname: Muller
authors.forename: Warner S
authors.initials: WS
authors.lastname: Simonides
mesh_terms: D000818:Animals; D006332:Cardiomegaly / Q000150:complications / Q000378:metabolism* / Q000503:physiopathology; D006333:Heart Failure / Q000209:etiology / Q000378:metabolism; D006352:Heart Ventricles / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D007453:Iodide Peroxidase / Q000235:genetics / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000378:metabolism*; D051381:Rats; D015398:Signal Transduction; D013963:Thyroid Hormones / Q000378:metabolism*
chemical_list: D013963:Thyroid Hormones; C117274:iodothyronine deiodinase type III; D007453:Iodide Peroxidase