Deiodinase Expression in a Rodent Model of Myocardial Infarction

Abstract

Serum triiodothyronine (T3) concentration is reduced in patients with congestive heart failure which may contribute to altered T3 dependent gene expression and cell signaling. This effect could be due to an increase in type III deiodinase (D3) activity. D3 is a fetal enzyme that inactivates thyroxine as well as T3. We hypothesized that myocardial D3 expression would increase in a rodent model of myocardial infarction (MI) and attenuate activation of serine/threonine‐specific protein kinases (Akt) and endothelial nitric oxide synthase (eNOS). Echocardiography was used to assess left ventricular (LV) structure and function in male Sprague Dawley rats before and after coronary artery ligation. One week post‐MI, D3 expression was significantly increased while serum T3 and T4 were attenuated, (90.1±5.7 vs. 74.4±2.2ng/dL) and (4.54±0.15 vs. 4.17±0.10ug/dL), respectively. Additionally, Akt and eNOS activation were reduced as early as 3‐days post‐MI. By 7wks, serum T3 and T4 concentrations were no longer significantly different; however, LV systolic and diastolic volumes progressively increased over the 9wk study. Importantly, D3 expression remained elevated at 9wks. These findings support the hypothesis that myocardial D3 expression is increased and downstream targets of T3 may be attenuated after a myocardial infarction. Funding: Ralph and Marian Falk Medical Research Trust and King Pharmaceuticals.