title: Left-ventricular remodeling after myocardial infarction is associated with a cardiomyocyte-specific hypothyroid condition.
abstract: Similarities in cardiac gene expression in hypothyroidism and left ventricular (LV) pathological remodeling after myocardial infarction (MI) suggest a role for impaired cardiac thyroid hormone (TH) signaling in the development of heart failure. Increased ventricular activity of the TH-degrading enzyme type 3 deiodinase (D3) is recognized as a potential cause. In the present study, we investigated the cardiac expression and activity of D3 over an 8-wk period after MI in C57Bl/6J mice. Pathological remodeling of the noninfarcted part of the LV was evident from cardiomyocyte hypertrophy, interstitial fibrosis, and impairment of contractility. These changes were maximal and stable from the first week onward, as was the degree of LV dilation. A strong induction of D3 activity was found, which was similarly stable for the period examined. Plasma T(4) levels were transiently decreased at 1 wk after MI, but T(3) levels remained normal. The high D3 activity was associated with increased D3 mRNA expression at 1 but not at 4 and 8 wk after MI. Immunohistochemistry localized D3 protein to cardiomyocytes. In vivo measurement of TH-dependent transcription activity in cardiomyocytes using a luciferase reporter assay indicated a 48% decrease in post-MI mice relative to sham-operated animals, and this was associated with a 50% decrease in LV tissue T(3) concentration. In conclusion, pathological ventricular remodeling after MI in the mouse leads to high and stable induction of D3 activity in cardiomyocytes and a local hypothyroid condition.
authors.affiliation: Laboratory for Physiology, Institute for Cardiovascular Research, Vrije Universiteit University Medical Center, 1081 HV Amsterdam, The Netherlands.
authors.forename: Christine J
authors.initials: CJ
authors.lastname: Pol
authors.forename: Alice
authors.initials: A
authors.lastname: Muller
authors.forename: Marian J
authors.initials: MJ
authors.lastname: Zuidwijk
authors.forename: Elza D
authors.initials: ED
authors.lastname: van Deel
authors.forename: Ellen
authors.initials: E
authors.lastname: Kaptein
authors.forename: Alessandro
authors.initials: A
authors.lastname: Saba
authors.forename: Maja
authors.initials: M
authors.lastname: Marchini
authors.forename: Riccardo
authors.initials: R
authors.lastname: Zucchi
authors.forename: Theo J
authors.initials: TJ
authors.lastname: Visser
authors.forename: Walter J
authors.initials: WJ
authors.lastname: Paulus
authors.forename: Dirk J
authors.initials: DJ
authors.lastname: Duncker
authors.forename: Warner S
authors.initials: WS
authors.lastname: Simonides
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002851:Chromatography, High Pressure Liquid; D005260:Female; D007037:Hypothyroidism / Q000378:metabolism*; D007453:Iodide Peroxidase / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009203:Myocardial Infarction / Q000503:physiopathology*; D032383:Myocytes, Cardiac / Q000378:metabolism*; D011897:Random Allocation; D013963:Thyroid Hormones / Q000378:metabolism; D020257:Ventricular Remodeling / Q000502:physiology*
chemical_list: D013963:Thyroid Hormones; D007453:Iodide Peroxidase