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Publication : Lethal Cardiomyopathy in Mice Lacking Transferrin Receptor in the Heart.

First Author  Xu W Year  2015
Journal  Cell Rep Volume  13
Issue  3 Pages  533-545
PubMed ID  26456827 Mgi Jnum  J:269850
Mgi Id  MGI:6274152 Doi  10.1016/j.celrep.2015.09.023
Citation  Xu W, et al. (2015) Lethal Cardiomyopathy in Mice Lacking Transferrin Receptor in the Heart. Cell Rep 13(3):533-545
abstractText  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.
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