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

Abstract 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 cardia...

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Autores principales:	Abitha Sukumaran, JuOae Chang, Murui Han, Shrutika Mintri, Ban-An Khaw, Jonghan Kim
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/a9a626961b9d43c795e471811889b3af
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spelling	oai:doaj.org-article:a9a626961b9d43c795e471811889b3af2021-12-02T15:05:11ZIron overload exacerbates age-associated cardiac hypertrophy in a mouse model of hemochromatosis10.1038/s41598-017-05810-22045-2322https://doaj.org/article/a9a626961b9d43c795e471811889b3af2017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-05810-2https://doaj.org/toc/2045-2322Abstract 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.Abitha SukumaranJuOae ChangMurui HanShrutika MintriBan-An KhawJonghan KimNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-10 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Abitha Sukumaran JuOae Chang Murui Han Shrutika Mintri Ban-An Khaw Jonghan Kim Iron overload exacerbates age-associated cardiac hypertrophy in a mouse model of hemochromatosis
description	Abstract 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.
format	article
author	Abitha Sukumaran JuOae Chang Murui Han Shrutika Mintri Ban-An Khaw Jonghan Kim
author_facet	Abitha Sukumaran JuOae Chang Murui Han Shrutika Mintri Ban-An Khaw Jonghan Kim
author_sort	Abitha Sukumaran
title	Iron overload exacerbates age-associated cardiac hypertrophy in a mouse model of hemochromatosis
title_short	Iron overload exacerbates age-associated cardiac hypertrophy in a mouse model of hemochromatosis
title_full	Iron overload exacerbates age-associated cardiac hypertrophy in a mouse model of hemochromatosis
title_fullStr	Iron overload exacerbates age-associated cardiac hypertrophy in a mouse model of hemochromatosis
title_full_unstemmed	Iron overload exacerbates age-associated cardiac hypertrophy in a mouse model of hemochromatosis
title_sort	iron overload exacerbates age-associated cardiac hypertrophy in a mouse model of hemochromatosis
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/a9a626961b9d43c795e471811889b3af
work_keys_str_mv	AT abithasukumaran ironoverloadexacerbatesageassociatedcardiachypertrophyinamousemodelofhemochromatosis AT juoaechang ironoverloadexacerbatesageassociatedcardiachypertrophyinamousemodelofhemochromatosis AT muruihan ironoverloadexacerbatesageassociatedcardiachypertrophyinamousemodelofhemochromatosis AT shrutikamintri ironoverloadexacerbatesageassociatedcardiachypertrophyinamousemodelofhemochromatosis AT banankhaw ironoverloadexacerbatesageassociatedcardiachypertrophyinamousemodelofhemochromatosis AT jonghankim ironoverloadexacerbatesageassociatedcardiachypertrophyinamousemodelofhemochromatosis
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Iron overload exacerbates age-associated cardiac hypertrophy in a mouse model of hemochromatosis

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