title: Effects of Iron Overload on Cardiac Calcium Regulation: Translational Insights Into Mechanisms and Management of a Global Epidemic.
abstract: Iron overload cardiomyopathy occurs in a rare primary form (ie, hemochromatosis) and a very common secondary form in a host of hemoglobinopathies (eg, thalassemia, sickle cell anemia) of substantial and growing global prevalence, which have transformed iron overload cardiomyopathy into a worldwide epidemic. Intracellular calcium ([Ca(2+)]i) is known to be a critical regulator of myocardial function, in which it plays a key role in maintaining cardiac excitation-contraction coupling. It has been proposed that a disturbance in cardiac calcium regulation is a major contributor to left ventricular dysfunction in iron overload cardiomyopathy. This review comprehensively summarizes reports concerned with the effects of iron overload on cardiac calcium regulation, including alteration in the intracellular calcium level, voltage-gated calcium channel function, and calcium cycling protein activity. Consistent reports, as well as inconsistent findings, from both in vitro and in vivo studies, are presented and discussed. The understanding of these mechanisms has provided important new pathophysiological insights and has led to the development of novel therapeutic and preventive strategies for patients with iron overload cardiomyopathy that are currently in clinical trials.
authors: Cardiac Electrophysiology Research and Training Center, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand; Cardiac Electrophysiology Unit, Department of Physiology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand; Center of Excellence in Cardiac Electrophysiology Research, Chiang Mai University, Chiang Mai, Thailand.
authors: Juthamas
authors: J
authors: Khamseekaew
authors: Cardiac Electrophysiology Research and Training Center, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand; Cardiac Electrophysiology Unit, Department of Physiology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand; Center of Excellence in Cardiac Electrophysiology Research, Chiang Mai University, Chiang Mai, Thailand.
authors: Sirinart
authors: S
authors: Kumfu
authors: Cardiac Electrophysiology Research and Training Center, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand; Center of Excellence in Cardiac Electrophysiology Research, Chiang Mai University, Chiang Mai, Thailand; Department of Oral Biology and Diagnostic Sciences, Faculty of Dentistry, Chiang Mai University, Chiang Mai, Thailand.
authors: Siriporn C
authors: SC
authors: Chattipakorn
authors: Cardiac Electrophysiology Research and Training Center, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand; Cardiac Electrophysiology Unit, Department of Physiology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand; Center of Excellence in Cardiac Electrophysiology Research, Chiang Mai University, Chiang Mai, Thailand. Electronic address: nchattip@gmail.com.
authors: Nipon
authors: N
authors: Chattipakorn
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000378:metabolism; D009202:Cardiomyopathies / Q000378:metabolism* / Q000503:physiopathology; D006801:Humans; D019190:Iron Overload / Q000378:metabolism* / Q000503:physiopathology; D009200:Myocardial Contraction / Q000502:physiology; D032383:Myocytes, Cardiac / Q000378:metabolism
chemical_list: D015220:Calcium Channels; D002135:Calcium-Binding Proteins; D002118:Calcium