A Mouse Model of Cardiomyopathy Induced by Mutations in the Hemochromatosis HFE Gene

Does the age of patients with hereditary hemochromatosis at the moment of their first diagnosis have an additional effect on the standard echocardiographic parameters?

“…The results may even indirectly indicate a faster "heart aging" process in people with HH. Data from other studies support this hypothesis [20][21]. Using a mouse model of HH, Djemai et al suggested a correlation between cardiomyopathy and cardiac iron deposition with aging in mice homozygous for the C282Y HFE gene [20].…”

“…Data from other studies support this hypothesis [20][21]. Using a mouse model of HH, Djemai et al suggested a correlation between cardiomyopathy and cardiac iron deposition with aging in mice homozygous for the C282Y HFE gene [20]. Similarly, using another HH mouse model, Sukumaran et al demonstrated that cardiac iron loading can accelerate the natural aging process of the heart, especially cardiac hypertrophy and fibrosis and potentially heart failure [21].…”

Hemochromatosis Protein (HFE) Knockout Mice As a Novel Model of Hemochromatosis: Implications for Study and Management of Iron-Overload Cardiomyopathy

“…13 To date, murine models of iron-overload cardiomyopathy, such as wild-type mice injected with iron dextran, or HJV e/e on iron-rich diets, reproduce many phenotypic features seen in patients with iron-overload cardiomyopathy, but not systolic dysfunction. 8,[14][15][16] In this issue of the Canadian Journal of Cardiology, Djemai et al 17 demonstrate that aging in the HFE knockout (HFE e/ e ) murine model of primary hemochromatosis, in which iron overload is achieved through dietary iron uptake, results in iron-overload cardiomyopathy. Similar to patients with primary hemochromatosis, HFE e/e mice lack proper activity of the HFE protein, which leads to low levels of hepcidin and accumulation of iron from dietary sources.…”

“…[10][11][12] Use of adequate preclinical models such as the HFE e/e model as presented by Djemai et al 17 or the HJV e/e model, or both, 8,16 will be important in the development of safe and effective chelators and other emerging therapies such as amlodipine, 14,27 for which a phase II clinical trial has recently been successfully completed, as well as resveratrol. 16,28 Phenotypical similarities of the HFE e/e model presented by Djemai et al 17 to the clinical phenotype found in patients presents an opportunity to better clarify the contributions of various molecular mechanisms in the development of iron-overload injury, which occurs in response to increased levels of plasma and tissue iron. Unrestricted iron uptake (primary hemochromatosis) or the frequent use of blood transfusions (secondary iron overload) leads to accumulation of iron by transferrin and ferritin.…”