Name: SABRINA BERTOLI RODRIGUES
Publication date: 29/09/2023
Examining board:
Name |
Role |
|---|---|
| LEONARDO DOS SANTOS | Presidente |
| LORENA BARROS FURIERI | Examinador Interno |
| LUCIANA VENTURI ROSSONI | Examinador Externo |
| NAZARE SOUZA BISSOLI | Examinador Interno |
| PAULO CALEB JÚNIOR DE LIMA SANTOS | Examinador Externo |
Summary: Iron is an essential mineral for several cellular processes, mainly due to its ability to
participate in reactions in which it receives or donates electrons. For the same
reason, when free and in excess, it is a great precursor in the generation of reactive
oxygen species, damaging tissues, organs and systems. Several studies
demonstrate that iron overload is capable of causing cardiovascular damage, and a
probable relationship between the level of body iron and coronary artery disease has
even been suggested. In this study, we aimed to test the hypothesis that chronic iron
overload, per se, causes damage to the coronary vasculature, associated with the
generated oxidative stress and endothelial dysfunction. Serum, tissues and coronary
vessels of male Wistar rats from the Ct and Fe groups were analyzed, in which saline
solution (NaCl 0.9%) or iron-dextran (200 mg/kg/day) were administered
intraperitoneally, respectively, 5 times a week for 28 days. After euthanasia, blood
and organs were collected to assess serum and tissue iron, and vasoreactivity,
fluorescence for reactive oxygen species and nitric oxide, histolomorphometry were
performed in isolated coronary arteries. Finally, the modified Langedorff technique to
assess the coronary bed was performed in a new set of experimental rats. As
expected, iron overload increased serum and tissue iron levels, as well as reduced
the weight gain of animals in the Fe group compared to the Ct group. Furthermore,
there was an increase in reactivity and a reduction in the vasodilator response in the
isolated rings of coronary arteries in the Fe group, associated with an increase in the
generation of superoxide anion, probably mediated by the AT1 receptor. Iron overload
also significantly reduced the bioavailability of nitric oxide in the coronary arteries. In
addition to functional alterations, remodeling of arteries in the iron group was
observed, with collagen deposits and the presence of perivascular macrophages;
together with this, alteration of the vascular endothelium with cell detachment was
evidenced, which suggests a denudation of this layer. In the analysis of the isolated
coronary vascular bed, an increase in coronary perfusion pressure was observed in
this same Fe group, probably as a consequence of the increase in vascular
resistance and vasculopathy from iron overload. Our results demonstrate that chronic
iron overload induces coronary endothelial dysfunction, probably due to oxidative
stress and the imbalance between relaxing and contractile factors synthesized by the
damaged endothelium.
