title: Cardiomyopathy associated with iron overload: how does iron enter myocytes and what are the implications for pharmacological therapy?
abstract: Iron overload cardiomyopathy is one of the most common causes of death in thalassemia patients. Although new iron chelating agents have been developed, the mortality rate from heart failure remains elevated as a result of iron overload. This could be due to the fact that our understanding of the underlying mechanism of iron uptake into cardiomyocytes is still unclear, thus impeding the discovery and refinement of more effective therapy for thalassemia therapeutic strategies in thalassemic iron overload cardiomyopathy. Growing evidence indicates that multiple routes of iron entry into cardiomyocytes exist under iron overload conditions. These include both L-type (LTCC) and T-type (TTCC) calcium channels, divalent metal transporter 1 (DMT1) and transferrin receptors (TfRs). In this review, the routes of iron uptake into cardiomyocytes under iron overload conditions are presented. Evidence from pharmacological interventions in support or against the possible route of iron entry of each portal in cardiomyocytes are also comprehensively summarized and discussed.
authors.affiliation: Cardiac Electrophysiology Research and Training Center, Faculty of Medicine, Chiang Mai University , Chiang Mai , Thailand .
authors.forename: Karn
authors.initials: K
authors.lastname: Wijarnpreecha
authors.forename: Sirinart
authors.initials: S
authors.lastname: Kumfu
authors.forename: Siriporn C
authors.initials: SC
authors.lastname: Chattipakorn
authors.forename: Nipon
authors.initials: N
authors.lastname: Chattipakorn
mesh_terms: D000818:Animals; D015220:Calcium Channels / Q000378:metabolism; D009202:Cardiomyopathies / Q000150:complications* / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D006801:Humans; D007501:Iron / Q000378:metabolism*; D019190:Iron Overload / Q000150:complications* / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D013789:Thalassemia / Q000150:complications
chemical_list: D015220:Calcium Channels; D007501:Iron
keywords: Calcium channel; cardiomyopathy; iron overload; iron uptake; thalassemia