Discordance between biomarkers of iron status in plasma and myocardium across iron replete, iron deficiency, and iron replacement states.

Abstract

It is unclear whether plasma measures of iron status reflect iron status in tissues. This study compared the effects of iron deficiency or treatment with intravenous iron on plasma versus myocardial measures of iron metabolism and mitochondrial dysfunction in mice and humans. The human study included 31 people undergoing cardiac surgery. Twenty-two (71%) were iron deficient. The mouse study included 88 mice randomly allocated to iron replete diet group (Controls, n=29), an Iron Deficient diet (n=31) or an iron deficient diet followed by IV Iron administration (n=28). Outcomes included plasma iron and ferritin concentrations, and myocardial total iron, ferritin, IRP1 binding, and mitochondrial complex activity and DNA damage. In the human study, plasma ferritin positively correlated with myocardial ferritin (r2=0.155, p=0.012). People with iron deficiency had significantly lower myocardial ferritin levels than those without iron deficiency. There were no differences or significant correlations for other outcomes. In the mouse study, plasma ferritin negatively correlated with myocardial ferritin (r2=0.113, p=0.004), and iron deficiency reduced myocardial ferritin levels (p=0.018) as well as the binding affinity of myocardial IRP1 to the Ferritin heavy chain mRNA (p=0.033). Intravenous iron had divergent effects on plasma (increased) and myocardial (decreased) ferritin levels, and increased IRP1 binding affinity and mitochondrial respiratory complex activity (p=0.049). These finding suggest that measures of iron metabolism and iron deficiency in plasma do not consistently reflect myocardial iron status across iron replete, iron deficient, and iron replacement states.