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Reference: Lakhal-Littleton, S, Wolna, M, Carr, C et al., (2015). Cardiac ferroportin regulates cellular iron homeostasis and is important for cardiac function. Proceedings of the National Academy of Sciences, 112 (10), 3164-3169.Citable link to this page:

 

Cardiac ferroportin regulates cellular iron homeostasis and is important for cardiac function

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.

Peer Review status:Peer reviewedPublication status:PublishedVersion:Publisher's version Funder: British Heart Foundation   Funder: Vifor Pharma   Notes:"The author(s) retain copyright to individual articles, and the National Academy of Sciences of the United States of America retains an exclusive license to publish these articles and holds copyright to the collective work." This is the publisher's version of the article. The final version is available online from the National Academy of Sciences at: [10.1073/pnas.1422373112]

Bibliographic Details

Publisher: National Academy of Sciences

Publisher Website: http://www.nas.edu/

Journal: Proceedings of the National Academy of Sciencessee more from them

Publication Website: http://www.pnas.org/

Issue Date: 2015-02-23

pages:3164-3169Identifiers

Urn: uuid:ac64a102-d94d-4b00-a53a-d9995414de60

Source identifier: 508355

Eissn: 1091-6490

Doi: https://doi.org/10.1073/pnas.1422373112

Issn: 0027-8424 Item Description

Type: Journal article;

Language: eng

Version: Publisher's versionKeywords: Heart Animals Mice, Inbred C57BL Mice, Knockout Mice Iron Cation Transport Proteins Homeostasis Tiny URL: pubs:508355

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Author: Lakhal-Littleton, S - institutionUniversity of Oxford Oxford, MSD, Physiology Anatomy and Genetics - - - Wolna, M - institutionUn

Source: https://ora.ox.ac.uk/objects/uuid:ac64a102-d94d-4b00-a53a-d9995414de60



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