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.