Lethal Cardiomyopathy in Mice Lacking Transferrin Receptor in the Heart.

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Xu, W; Barrientos, T; Mao, L; Rockman, HA; Sauve, AA; Andrews, NC

Published Date

  • October 20, 2015

Published In

Volume / Issue

  • 13 / 3

Start / End Page

  • 533 - 545

PubMed ID

  • 26456827

Pubmed Central ID

  • PMC4618069

Electronic International Standard Serial Number (EISSN)

  • 2211-1247

Digital Object Identifier (DOI)

  • 10.1016/j.celrep.2015.09.023


  • eng

Conference Location

  • United States