Background/aims: Intravenous (IV) iron preparations are widely used in the management of anemia in ESRD populations. Recent changes in reimbursement policy have dramatically increased the use of IV iron to lower the use of costly erythropoiesis-stimulating agents. These preparations are frequently administered with insufficient attention to the total body iron stores or presence of inflammation which is aggravated by excess iron. Endothelial injury and dysfunction are critical steps in atherosclerosis, thrombosis and cardiovascular disease. IV iron preparations raise plasma non-transferrin-bound iron which can promote oxidative stress, endothelial damage and dysfunction. We explored the effect of an IV iron preparation on endothelial cells, monocytes and isolated arteries.

Methods: Primary cultures of human aortic endothelial cells (HAEC) were treated with pharmacologically relevant concentrations of iron sucrose (10-100 μg/ml) for 4-24 h. Endothelial cell morphology, viability, and monocyte adhesion were tested. Endothelial function was assessed by measuring the vasorelaxation response to acetylcholine in normal rat thoracic aorta rings preincubated with iron sucrose (200 μg/ml).

Results: In contrast to the control HAEC which showed normal cobblestone appearance, cells treated with iron sucrose (50-100 μg/ml) for 4 h showed loss of normal morphological characteristics, cellular fragmentation, shrinkage, detachment, monolayer disruption and nuclear condensation/fragmentation features signifying apoptosis. HAEC exposure to iron sucrose (10-100 μg/ml) increased monocyte adhesion 5- to 25-fold. Incubation in media containing 200 μg/ml iron sucrose for 3 h caused marked reduction in the acetylcholine-mediated relaxation in phenylephrine-precontracted rat aorta.

Conclusion: Pharmacologically relevant concentration of iron sucrose results in endothelial injury and dysfunction and marked increase in monocyte adhesion.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3265804PMC
http://dx.doi.org/10.1159/000334939DOI Listing

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