1. Lethal Cardiomyopathy in Mice Lacking Transferrin Receptor in the Heart.
- Author
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Xu W, Barrientos T, Mao L, Rockman HA, Sauve AA, and Andrews NC
- Subjects
- Animals, Cardiomyopathies drug therapy, Cardiomyopathies pathology, Cell Respiration, Iron metabolism, Mice, Mitophagy, Myocardium pathology, Niacinamide analogs & derivatives, Niacinamide therapeutic use, Pyridinium Compounds, Receptors, Transferrin metabolism, Cardiomyopathies genetics, Myocardium metabolism, Receptors, Transferrin genetics
- Abstract
Both iron overload and iron deficiency have been associated with cardiomyopathy and heart failure, but cardiac iron utilization is incompletely understood. We hypothesized that the transferrin receptor (Tfr1) might play a role in cardiac iron uptake and used gene targeting to examine the role of Tfr1 in vivo. Surprisingly, we found that decreased iron, due to inactivation of Tfr1, was associated with severe cardiac consequences. Mice lacking Tfr1 in the heart died in the second week of life and had cardiomegaly, poor cardiac function, failure of mitochondrial respiration, and ineffective mitophagy. The phenotype could only be rescued by aggressive iron therapy, but it was ameliorated by administration of nicotinamide riboside, an NAD precursor. Our findings underscore the importance of both Tfr1 and iron in the heart, and may inform therapy for patients with heart failure., (Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.)
- Published
- 2015
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