Influence of mitochondrial and systemic iron levels in heart failure pathology.

Abstract

Iron deficiency or overload poses an increasingly complex issue in cardiovascular disease, especially heart failure. The potential benefits and side effects of iron supplementation are still a matter of concern, even though current guidelines suggest therapeutic management of iron deficiency. In this review, we sought to examine the iron metabolism and to identify the rationale behind iron supplementation and iron chelation. Cardiovascular disease is increasingly linked with iron dysmetabolism, with an increased proportion of heart failure patients being affected by decreased plasma iron levels and in turn, by the decreased quality of life. Multiple studies have concluded on a benefit of iron administration, even if just for symptomatic relief. However, new studies field evidence for negative effects of dysregulated non-bound iron and its reactive oxygen species production, with concern to heart diseases. The molecular targets of iron usage, such as the mitochondria, are prone to deleterious effects of the polyvalent metal, added by the scarcely described processes of iron elimination. Iron supplementation and iron chelation show promise of therapeutic benefit in heart failure, with the extent and mechanisms of both prospects not being entirely understood. It may be that a state of decreased systemic and increased mitochondrial iron levels proves to be a useful frame for future advancements in understanding the interconnection of heart failure and iron metabolism.