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Involvement of cytosolic and mitochondrial iron in iron overload cardiomyopathy: an update

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Abstract

Iron overload cardiomyopathy (IOC) is a major cause of death in patients with diseases associated with chronic anemia such as thalassemia or sickle cell disease after chronic blood transfusions. Associated with iron overload conditions, there is excess free iron that enters cardiomyocytes through both L- and T-type calcium channels thereby resulting in increased reactive oxygen species being generated via Haber-Weiss and Fenton reactions. It is thought that an increase in reactive oxygen species contributes to high morbidity and mortality rates. Recent studies have, however, suggested that it is iron overload in mitochondria that contributes to cellular oxidative stress, mitochondrial damage, cardiac arrhythmias, as well as the development of cardiomyopathy. Iron chelators, antioxidants, and/or calcium channel blockers have been demonstrated to prevent and ameliorate cardiac dysfunction in animal models as well as in patients suffering from cardiac iron overload. Hence, either a mono-therapy or combination therapies with any of the aforementioned agents may serve as a novel treatment in iron-overload patients in the near future. In the present article, we review the mechanisms of cytosolic and/or mitochondrial iron load in the heart which may contribute synergistically or independently to the development of iron-associated cardiomyopathy. We also review available as well as potential future novel treatments.

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Acknowledgements

This work was supported by the National Institute of Health (R01s HL97979 and HL133294 to LHX), American Heart Association (Grant-in-Aid to LHX), the National Science and Technology Development Agency Thailand (NSTDA Research Chair grant to NC), and the Thailand Research Fund (RTA6080003 to SCC and RGJ to SCC and SW).

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  1. Richard Gordan and Suwakon Wongjaikam contributed equally to this work.

Authors and Affiliations

  1. Department of Cell Biology and Molecular Medicine, Rutgers University-New Jersey Medical School, Newark, New Jersey, 07103, USA

    Richard Gordan, Judith K. Gwathmey & Lai-Hua Xie

  2. Cardiac Electrophysiology Research and Training Center, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand

    Suwakon Wongjaikam, Nipon Chattipakorn & Siriporn C. Chattipakorn

  3. Cardiac Electrophysiology Unit, Department of Physiology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand

    Suwakon Wongjaikam & Nipon Chattipakorn

  4. Center of Excellence in Cardiac Electrophysiology Research, Chiang Mai University, Chiang Mai, Thailand

    Suwakon Wongjaikam, Nipon Chattipakorn & Siriporn C. Chattipakorn

  5. Gwathmey Inc., Cambridge, Massachusetts, USA

    Judith K. Gwathmey

  6. Department of Oral Biology and Diagnostic Sciences, Faculty of Dentistry, Chiang Mai University, Chiang Mai, Thailand

    Siriporn C. Chattipakorn

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Gordan, R., Wongjaikam, S., Gwathmey, J.K. et al. Involvement of cytosolic and mitochondrial iron in iron overload cardiomyopathy: an update. Heart Fail Rev 23, 801–816 (2018). https://doi.org/10.1007/s10741-018-9700-5

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