Getting to the "Heart" of Cardiac Disease by Decreasing Mitochondrial Iron.

Abstract

Iron chelation rather than supplementation would be beneficial to patients with heart diseases. More effort should be devoted to the development of iron chelators that could target mitochondrial iron. Iron is an essential trace mineral for normal mammalian physiology. It is incorporated into iron/sulfur (Fe/S) clusters that serve as important cofactors for many enzymes, including the mitochondrial respiratory chain, and it gives blood and muscle their signature red color through its presence in heme.1 Because of its involvement in many important cellular processes, dysregulation of iron often causes disease. There are 2 broad categories of diseases associated with iron dysregulation—iron overload and iron deficiency. Each category can be further subdivided based on whether the changes in iron occur at the cellular or at the systemic level. Iron is critical for developmental processes, and studies have linked severe systemic iron deficiency to impaired brain development in children.2 However, most of these studies were conducted in developing countries where iron deficiency tends to be more severe. In developed countries, the major disorder associated with iron deficiency is anemia. Although systemic iron deficiency and anemia may have been used interchangeably, these 2 terms refer to different conditions. Systemic iron deficiency refers to low amounts of iron in circulation because of limited iron absorption or excess iron loss. Anemia is defined as low hemoglobin content within red blood cells and can be caused by low systemic iron, mutations in hemoglobin genes, vitamin B12 deficiency, or underlying chronic diseases. Limited oxygen-carrying capacity secondary to anemia can cause fatigue; however, it generally does not cause mortality or major damage to vital organs. Except for high-output heart failure (HF) associated with severe anemia, iron deficiency and anemia are not associated with any other major cardiac disorders. Cellular iron deficiency is a rare phenomenon, and except …