Iron Metabolism in Cardiovascular Disease: Physiology, Mechanisms, and Therapeutic Targets
Konrad Teodor Sawicki1,2, Adam De Jesus1, Hossein Ardehali1,2
1Feinberg Cardiovascular and Renal Research Institute (K.T.S., A.D.J., H.A.), Feinberg School of Medicine, Northwestern University, Chicago, IL.
Insights
Iron is vital for heart health but too much or too little harms it. Understanding iron balance is key for treating cardiovascular diseases and using iron therapy effectively.
Area of Science:
- Cardiovascular Physiology
- Iron Metabolism
- Biochemistry
Background:
- Iron is essential for the cardiovascular system's energy demands, oxygen transport, and mitochondrial function.
- Both iron deficiency and overload can negatively impact cardiovascular health, leading to conditions like heart failure and myocardial infarction.
- The cardiovascular system's sensitivity to iron overload is exacerbated by having limited iron export mechanisms.
Purpose of the Study:
- To provide a comprehensive overview of iron homeostasis within the cardiovascular system.
- To discuss the implications of iron dysregulation in various cardiovascular diseases.
- To review current and future therapeutic strategies for managing iron levels in cardiovascular conditions.
Main Methods:
- Literature review of systemic and cellular iron metabolism.
- Analysis of iron's role in cardiovascular physiology and pathology.
- Examination of current therapeutic approaches, including intravenous iron therapy.
Main Results:
- Iron homeostasis is tightly regulated, yet dysregulation is implicated in numerous cardiovascular diseases.
- Iron deficiency and overload present distinct challenges to cardiovascular health.
- Intravenous iron therapy is emerging as a treatment option for specific patient groups with heart failure.
Conclusions:
- Maintaining iron homeostasis is crucial for cardiovascular health.
- Further research into iron metabolism is needed to develop effective treatments for cardiovascular diseases.
- Personalized therapeutic strategies targeting iron levels hold promise for improving cardiovascular outcomes.
Abstract:
The cardiovascular system requires iron to maintain its high energy demands and metabolic activity. Iron plays a critical role in oxygen transport and storage, mitochondrial function, and enzyme activity. However, excess iron is also cardiotoxic due to its ability to catalyze the formation of reactive oxygen species and promote oxidative damage. While mammalian cells have several redundant iron import mechanisms, they are equipped with a single iron-exporting protein, which makes the cardiovascular system particularly sensitive to iron overload. As a result, iron levels are tightly regulated at many levels to maintain homeostasis. Iron dysregulation ranges from iron deficiency to iron overload and is seen in many types of cardiovascular disease, including heart failure, myocardial infarction, anthracycline-induced cardiotoxicity, and Friedreich's ataxia. Recently, the use of intravenous iron therapy has been advocated in patients with heart failure and certain criteria for iron deficiency. Here, we provide an overview of systemic and cellular iron homeostasis in the context of cardiovascular physiology, iron deficiency, and iron overload in cardiovascular disease, current therapeutic strategies, and future perspectives.
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