Stored Iron and Vascular Reactivity

Abstract

Zheng et al1 report that volunteer blood donors with a high donation frequency have significantly greater flow-mediated dilation than low frequency donors. Iron status among the frequent donors approximated a state of iron depletion by assessment of conventional iron markers. The study provides important support for the “iron hypothesis,” which suggests a protective effect of iron depletion, ie, the absence of storage iron without anemia, against ischemic heart disease.2–4 The blood donor findings suggest a new direction for the study of endothelial iron status in vivo to complement a growing body of work on iron in cultured endothelial cells. In addition, the finding of lower serum nitrotyrosine in frequent donors is consistent with the hypothesis that myeloperoxidase, a powerful emerging cardiovascular risk factor,5–8 is modifiable by manipulation of iron status. See page 1577 In cultured endothelial cells, iron status can be readily manipulated through the use of iron chelators or supplemental iron,9 or by altering the essential fatty acid composition of the culture medium.10 Use of these methods has identified several important effects of iron in endothelial activation and oxidative injury.9,11–20 But the in vitro approach does not define endothelial iron status in vivo, in particular what might represent a physiologically optimal range of endothelial iron concentrations. Iron status parameters such as serum ferritin are imperfect measures of total body iron stores and are likely to be even less adequate in assessing endothelial iron status. There is the additional uncertainty of differences in storage iron concentration in various cell types, even in situations in which total body iron status is well defined. An important premise of the study by Zheng et al1 is that body iron status within the conventionally defined normal range can influence endothelial iron status and endothelial function in vivo. …