Abstract P138: The Arterial Wall of the Central Vascular Compartment a Novel Target of Iron-Overload Disorders: A Preliminary Study With Experimental Correlation in Animals

Abstract

In Hemochromatosis (H) iron is stored in tissues, causing organ injury and failure. Patients with H have a shorter life expectancy and an increase in CVR. Our group could prove that arterial stiffness was increased and they had added endothelial dysfunction. After that we also were able to demonstrate that both improve by reducing iron levels with phlebotomies. Due to these findings we ask how iron-overload made it (getting inside or more likely inducing inflammation). Anyway either directly or indirectly AW could be a target of iron-overload. To test this hypothesis we did an experimental correlation by using a known model of H in rats and we analize histologically the AW Twelve young rats (3 months old), an average weight of 300 gr, fed as usual, in individual cages with dark light cycles of 12 h and controlled temperature (22±3°C), were ramdonly divided in 2 groups: 1) Iron-overoload group (IOG). They were daily administrated intraperitoneally 10 mg of elemental iron (0,1 ml of dextran iron, Venofer®) 12 injections in total 2) Control group (CG) the same injections scheme but with placebo. The handlings of animals was under the norms of the bioterium and standards designed for that purpose. At the end of experimental period (8 weeks) animals were sacrificed and studied. The histoarchitecture of the proximal aortic wall (fixed in 4 % formalin, paraffin-embedded, sectioned into thin slices, H&E, Masson′s trichrome and VVG staining) showed no significant differences in the histology (H&E) between IOG and CG. No evidence of iron inside the AW. On the other hand inflammatory component was significantly increased in IOG compared to CG, perivascular lymphocyte count 5-12/0 IOG/CG, perivascular macrophages, 3-5/0 IOG/CG. Elastic fibers were not fragmented but become thin and lost their disposition in IOG. In conclusions we can affirm that AW could represent a novel target in H and could may the nexus to cardiovascular disease. The indirect mechanism (inflammation and elastic fibers) explains why previously improved after phlebotomies. Our findings supports future research including inflammatory mediators and their tissue expression, and extend them to others iron overload disorders.