Efeitos da sobrecarga crônica de ferro sobre a estrutura e função de artéria coronária de ratos

• Ano de defesa: 2023
• Autor(a) principal: Rodrigues, Sabrina Bertoli
• Tipo de documento: Tese
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade Federal do Espírito Santo; BR; Doutorado em Ciências Fisiológicas; Centro de Ciências da Saúde; UFES; Programa de Pós-Graduação em Ciências Fisiológicas
• Palavras-chave em Português: Ferro; Sobrecarga de ferro; Coronária; Reatividadevascular; Espécies reativas de oxigênio; Endotélio; subject.br-rjbn; Fisiologia
• Link de acesso: http://repositorio.ufes.br/handle/10/17220

Iron is an essential mineral for several cellular processes, mainly due toitsabilitytoparticipate in reactions in which it receives or donates electrons. For thesamereason, when free and in excess, it is a great precursor in the generationof reactiveoxygen species, damaging tissues, organs and systems. Several studiesdemonstrate that iron overload is capable of causing cardiovascular damage, andaprobable relationship between the level of body iron and coronary artery diseasehaseven been suggested. In this study, we aimed to test the hypothesis that chronicironoverload, per se, causes damage to the coronary vasculature, associatedwiththegenerated oxidative stress and endothelial dysfunction. Serum, tissues andcoronaryvessels of male Wistar rats from the Ct and Fe groups were analyzed, inwhichsalinesolution (NaCl 0.9%) or iron-dextran (200 mg/kg/day) were administeredintraperitoneally, respectively, 5 times a week for 28 days. After euthanasia, bloodand organs were collected to assess serum and tissue iron, and vasoreactivity,fluorescence for reactive oxygen species and nitric oxide, histolomorphometrywereperformed in isolated coronary arteries. Finally, the modified Langedorff techniquetoassess the coronary bed was performed in a new set of experimental rats. Asexpected, iron overload increased serum and tissue iron levels, as well asreducedthe 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 responseintheisolated rings of coronary arteries in the Fe group, associated with an increaseinthegeneration of superoxide anion, probably mediated by the AT1 receptor. Ironoverloadalso significantly reduced the bioavailability of nitric oxide in the coronary arteries. Inaddition to functional alterations, remodeling of arteries in the irongroupwasobserved, with collagen deposits and the presence of perivascular macrophages;together with this, alteration of the vascular endothelium with cell detachment wasevidenced, which suggests a denudation of this layer. In the analysis of theisolatedcoronary vascular bed, an increase in coronary perfusion pressure was observedinthis same Fe group, probably as a consequence of the increaseinvascularresistance and vasculopathy from iron overload. Our results demonstratethat chroniciron overload induces coronary endothelial dysfunction, probably duetooxidativestress and the imbalance between relaxing and contractile factors synthesizedbythedamaged endothelium.