Lethal Cardiomyopathy in Mice Lacking Transferrin Receptor in the Heart Academic Article uri icon

Overview

MeSH Major

  • Cardiomyopathies
  • Myocardium
  • Receptors, Transferrin

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.

publication date

  • January 2015

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed Central ID

  • PMC4618069

Digital Object Identifier (DOI)

  • 10.1016/j.celrep.2015.09.023

PubMed ID

  • 26456827

Additional Document Info

start page

  • 533

end page

  • 45

volume

  • 13

number

  • 3