Abstract 307: Fetal Deiodinase Increases in a Rodent Model of Myocardial Infarction
Rationale: Thyroid hormone (T3) has been shown to play a critical role in myocardial vascular homeostasis. Importantly, patients with congestive heart failure frequently have reduced serum T3 concentrations which may induce vascular rarefaction and/or limit angiogenesis during left ventricular remodeling. One possible mechanism for reducing T3 concentration is the reactivation of Type III deiodinase. Type III deiodinase (D3) is a fetal enzyme that inactivates thyroxine as well as T3.
Objective: Determine whether enzymes regulating myocardial thyroid hormone concentration are altered after a myocardial infarction.
Hypothesis: Myocardial D3 protein levels will increase in a rodent model of myocardial infarction, and immediate T3 supplementation will augment angiogenesis and adaptive left ventricular remodeling.
Methods and Results: The left anterior descending coronary artery was ligated in adult male Sprague Dawley rats with controls undergoing identical procedures without ligation. Osmotic mini-pumps were immediately implanted subcutaneously to deliver saline or T3 (10ug/kg/day). One week post-surgery, hearts were removed and subdivided into ischemic, border-zone, and non-infarcted/posterior wall. Results show that Type II deiodinase (D2) protein levels were increased in the ischemic zone of infarcted hearts (D2 is normally expressed in the heart and converts thyroxine into T3). D3 protein levels were also increased in the ischemic zone of MI-hearts. Importantly, the D2 to D3 ratio was reduced by ~60% suggesting T3 concentrations could be reduced in the ischemic regions of the heart. Additionally, D3 dimers were only present in the ischemic region of the MI heart. Because dimerization is thought to be required for enzymatic activity, ischemic areas of the heart may have regional hypothyroidism. Overall, these findings support the hypothesis that myocardial D3 protein levels are increased 7-days after a myocardial infarction.
Conclusion: The increase in dimerized D3 protein levels in the ischemic region of the heart may reduce local T3 concentrations and contribute to mal-adaptive left ventricular remodeling.
- © 2013 by American Heart Association, Inc.