41 Even term newborns typically undergo a brief period of high serum ferritin and transferrin saturation shortly after birth.

It has been proposed that this is attributable in part to features of iron metabolism in the neonatal period. Newborns, especially premature newborns, have increased susceptibility to oxidative injury. HUVEC are derived from umbilical vein, and as such could have endothelial iron levels higher than those encountered in other tissues at the time of harvesting because of regulatory factors involved in iron transfer from mother to fetus. However, there may be tissue specificities with respect to endothelial iron status. If the order of magnitude greater iron content of freshly prepared cells approximates in vivo conditions, might this higher level be typical of endothelial iron status in vivo? If so, the in vitro work seems to suggest that endothelial cells could be quite sensitive to oxidative injury in vivo. It is not clear whether iron content in freshly harvested HUVEC, or endothelial cells from other sources for that matter, accurately reflects iron content in vivo, or, perhaps is produced as an artifact of the conditions of harvesting. The magnitude of the changes in iron content with subculturing is commensurate with ranges of added iron shown, for example, to markedly influence production of adhesion molecules in cultured endothelial cells. 11,13 Large increases in cellular resistance to injury correlate closely with a steep fall in cellular iron content as a function of passage number. Sensitivity of HUVEC to oxidative injury or high glucose levels decreases sharply with subculture in vitro after a few passages. 22–40Ĭorrelation of in vitro with in vivo endothelial iron status will be assisted by future studies into the basis for an interesting phenomenon seen in human umbilical vein endothelial cells (HUVEC). 21 The small but growing literature on the effects of induced iron depletion/deficiency in various experimental models of oxidative or inflammatory injury strongly supports beneficial effects of eliminating storage iron. This view is related to the traditional acceptance of the safety of storage iron despite the lack of appropriate and definitive testing. However, there is a pervasive hidden assumption that endothelial function does not vary with iron status over a very wide but loosely defined range of “normal” stored iron concentrations. Alteration of endothelial function in extreme iron overload or severe iron deficiency would not be a surprise. 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.Īn important premise of the study by Zheng et al 1 is that body iron status within the conventionally defined normal range can influence endothelial iron status and endothelial function in vivo. 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.

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. 10 Use of these methods has identified several important effects of iron in endothelial activation and oxidative injury. 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. Customer Service and Ordering Information.Stroke: Vascular and Interventional Neurology.Journal of the American Heart Association (JAHA).Circ: Cardiovascular Quality & Outcomes.Arteriosclerosis, Thrombosis, and Vascular Biology (ATVB).

Iron reactivity