| Content Provider |
World Health Organization (WHO)-Global Index Medicus |
| Author |
Wolna, Magda Miller, Jack J. J. Ball, Vicky Holdship, Philip Lakhal-littleton, Samira Carr, Carolyn A. Stillion, Richard Davies, Benjamin Diaz, Rebeca Robbins, Peter A. Larner, Fiona Clarke, Kieran Christian, Helen C. Tyler, Damian J. Santos, Ana Biggs, Daniel |
| Description |
Author Affiliation: Lakhal-Littleton S ( Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford OX1 3PT, United Kingdom); Wolna M ( Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford OX1 3PT, United Kingdom); Carr CA ( Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford OX1 3PT, United Kingdom); Miller JJ ( Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford OX1 3PT, United Kingdom); Christian HC ( Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford OX1 3PT, United Kingdom); Ball V ( Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford OX1 3PT, United Kingdom); Santos A ( Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BH, United Kingdom); Diaz R ( Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BH, United Kingdom); Biggs D ( Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BH, United Kingdom); Stillion R ( Dunn School of Pathology, University of Oxford, Oxford OX1 3RF, United Kingdom); Holdship P ( Department of Earth Sciences, University of Oxford, Oxford OX1 3AN, United Kingdom.); Larner F ( Department of Earth Sciences, University of Oxford, Oxford OX1 3AN, United Kingdom.); Tyler DJ ( Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford OX1 3PT, United Kingdom); Clarke K ( Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford OX1 3PT, United Kingdom); Davies B ( Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BH, United Kingdom); Robbins PA ( Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford OX1 3PT, United Kingdom); |
| Abstract |
Iron is essential to the cell. Both iron deficiency and overload impinge negatively on cardiac health. Thus, effective iron homeostasis is important for cardiac function. Ferroportin (FPN), the only known mammalian iron-exporting protein, plays an essential role in iron homeostasis at the systemic level. It increases systemic iron availability by releasing iron from the cells of the duodenum, spleen, and liver, the sites of iron absorption, recycling, and storage respectively. However, FPN is also found in tissues with no known role in systemic iron handling, such as the heart, where its function remains unknown. To explore this function, we generated mice with a cardiomyocyte-specific deletion of Fpn. We show that these animals have severely impaired cardiac function, with a median survival of 22 wk, despite otherwise unaltered systemic iron status. We then compared their phenotype with that of ubiquitous hepcidin knockouts, a recognized model of the iron-loading disease hemochromatosis. The phenotype of the hepcidin knockouts was far milder, with normal survival up to 12 mo, despite far greater iron loading in the hearts. Histological examination demonstrated that, although cardiac iron accumulates within the cardiomyocytes of Fpn knockouts, it accumulates predominantly in other cell types in the hepcidin knockouts. We conclude, first, that cardiomyocyte FPN is essential for intracellular iron homeostasis and, second, that the site of deposition of iron within the heart determines the severity with which it affects cardiac function. Both findings have significant implications for the assessment and treatment of cardiac complications of iron dysregulation. |
| ISSN |
00278424 |
| e-ISSN |
10916490 |
| Journal |
Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number |
10 |
| Volume Number |
112 |
| Language |
English |
| Publisher |
National Academy of Sciences |
| Publisher Date |
2015-03-01 |
| Publisher Place |
United States |
| Access Restriction |
Open |
| Subject Keyword |
Cation Transport Proteins Physiology Heart Homeostasis Metabolism Animals Mice Mice, Inbred C57BL Mice, Knockout Research Support, Non-U.S. Gov't Multidisciplinary |
| Content Type |
Text |
| Resource Type |
Article |
| Subject |
Multidisciplinary |
