RGD Reference Report - Iron overload exacerbates age-associated cardiac hypertrophy in a mouse model of hemochromatosis. - Rat Genome Database

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Iron overload exacerbates age-associated cardiac hypertrophy in a mouse model of hemochromatosis.

Authors: Sukumaran, Abitha  Chang, JuOae  Han, Murui  Mintri, Shrutika  Khaw, Ban-An  Kim, Jonghan 
Citation: Sukumaran A, etal., Sci Rep. 2017 Jul 18;7(1):5756. doi: 10.1038/s41598-017-05810-2.
RGD ID: 14746969
Pubmed: PMID:28720890   (View Abstract at PubMed)
PMCID: PMC5516030   (View Article at PubMed Central)
DOI: DOI:10.1038/s41598-017-05810-2   (Journal Full-text)

Cardiac damage associated with iron overload is the most common cause of morbidity and mortality in patients with hereditary hemochromatosis, but the precise mechanisms leading to disease progression are largely unexplored. Here we investigated the effects of iron overload and age on cardiac hypertrophy using 1-, 5- and 12-month old Hfe-deficient mice, an animal model of hemochromatosis in humans. Cardiac iron levels increased progressively with age, which was exacerbated in Hfe-deficient mice. The heart/body weight ratios were greater in Hfe-deficient mice at 5- and 12-month old, compared with their age-matched wild-type controls. Cardiac hypertrophy in 12-month old Hfe-deficient mice was consistent with decreased alpha myosin and increased beta myosin heavy chains, suggesting an alpha-to-beta conversion with age. This was accompanied by cardiac fibrosis and up-regulation of NFAT-c2, reflecting increased calcineurin/NFAT signaling in myocyte hypertrophy. Moreover, there was an age-dependent increase in the cardiac isoprostane levels in Hfe-deficient mice, indicating elevated oxidative stress. Also, rats fed high-iron diet demonstrated increased heart-to-body weight ratios, alpha myosin heavy chain and cardiac isoprostane levels, suggesting that iron overload promotes oxidative stress and cardiac hypertrophy. Our findings provide a molecular basis for the progression of age-dependent cardiac stress exacerbated by iron overload hemochromatosis.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
HFEHumanCardiomegaly  ISOHfe (Mus musculus)associated with hemochromatosisRGD 
HfeRatCardiomegaly  ISOHfe (Mus musculus)associated with hemochromatosisRGD 
HfeMouseCardiomegaly  IMP associated with hemochromatosisRGD 

Objects Annotated

Genes (Rattus norvegicus)
Hfe  (homeostatic iron regulator)

Genes (Mus musculus)
Hfe  (homeostatic iron regulator)

Genes (Homo sapiens)
HFE  (homeostatic iron regulator)


Additional Information