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

Area of Science:

• Cardiology
• Hematology
• Toxicology

Background:

• Iron overload cardiomyopathy (IOC) is a significant cause of mortality in patients with chronic anemias like thalassemia and sickle cell disease, often resulting from frequent blood transfusions.
• Excess iron accumulation in cardiomyocytes leads to increased reactive oxygen species (ROS) production via Haber-Weiss and Fenton reactions, contributing to cardiac dysfunction.
• Emerging evidence highlights mitochondrial iron overload as a key driver of oxidative stress, mitochondrial damage, arrhythmias, and cardiomyopathy development.

Purpose of the Study:

• To review the mechanisms of cytosolic and mitochondrial iron accumulation in the heart.
• To explore how iron overload contributes to the development of iron-associated cardiomyopathy.
• To discuss current and potential future therapeutic strategies for IOC.

Main Methods:

• Review of existing literature on iron metabolism and cardiac function.
• Analysis of studies investigating iron transport into cardiomyocytes.
• Examination of research on the role of mitochondrial iron in cardiac pathology.

Main Results:

• Excess iron enters cardiomyocytes via L- and T-type calcium channels, generating ROS and contributing to cellular damage.
• Mitochondrial iron overload is strongly implicated in oxidative stress, mitochondrial dysfunction, and arrhythmogenesis.
• Iron chelators, antioxidants, and calcium channel blockers have shown efficacy in preclinical and clinical settings for ameliorating cardiac dysfunction.

Conclusions:

• Both cytosolic and mitochondrial iron overload can independently or synergistically contribute to the pathogenesis of IOC.
• Therapeutic interventions targeting iron chelation, oxidative stress, or calcium channels hold promise for novel treatments.
• Future research should focus on refining these therapies for improved patient outcomes in iron overload conditions.