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

• Published in: Heart failure reviews Vol. 23; no. 5; pp. 801 - 816
• Main Authors: Gordan, Richard, Wongjaikam, Suwakon, Gwathmey, Judith K., Chattipakorn, Nipon, Chattipakorn, Siriporn C., Xie, Lai-Hua
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.09.2018; Springer Nature B.V
• Subjects: Animal models; Animals; Antioxidants; Blood transfusion; Calcium channels; Calcium channels (T-type); Cardiology; Cardiomyocytes; Cardiomyopathies - etiology; Cardiomyopathies - metabolism; Cardiomyopathies - physiopathology; Cardiomyopathy; Chelating agents; Heart diseases; Humans; Iron; Iron Overload - complications; Iron Overload - metabolism; Medicine; Medicine & Public Health; Mitochondria; Morbidity; Myocytes, Cardiac - metabolism; Oxidative Stress; Patients; Reactive oxygen species; Reactive Oxygen Species - metabolism; Sickle cell disease; Thalassemia; Iron overload cardiomyopathy; Mitochondria; Animal models; Treatment; Cytosol
• ISSN: 1382-4147; 1573-7322
• DOI: 10.1007/s10741-018-9700-5

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.