Chronic iron overload intensifies atherosclerosis in apolipoprotein E deficient mice: Role of oxidative stress and endothelial dysfunction.
Life Sci
; 233: 116702, 2019 Sep 15.
Article
em En
| MEDLINE
| ID: mdl-31356905
ABSTRACT
AIMS:
We previously demonstrated that iron overload induces endothelial dysfunction and oxidative stress, which could increase the risk for atherosclerosis. However, the iron-related harmfulness under a genetic predisposition to atherosclerosis is still unclear. Here, we have tested the hypothesis that chronic iron overload may change vascular reactivity associated with worsening of the atherosclerotic process in apolipoprotein E knockout (apoE(-/-)) mice. MAINMETHODS:
Serum and aortas of wild-type (WT) and apoE(-/-) mice injected with iron-dextran (IO, 10â¯mg/mouse/day, ip) or saline 5 times a week for 4â¯weeks, were used. KEYFINDINGS:
Iron overload increased serum levels of iron and biomarkers of liver injury and oxidative stress, and iron deposition in the aorta in both lines, but only apoE(-/-) IO mice had intensified hypercholesterolemia and atherosclerosis. By scanning electron microscopy, the small endothelial structural damage caused by iron in WT was worsened in the apoE(-/-) group. However, endothelial dysfunction was found only in the apoE(-/-) IO group, identified by impaired relaxation to acetylcholine and hyperreactivity to phenylephrine associated with reduced nitric oxide modulation. Moreover, tiron and indomethacin attenuated reactivity to phenylephrine with greater magnitude in aortas of the apoE(-/-) IO group. Confirming, there were changes in the antioxidant (superoxide dismutase and catalase) activity, increased expression of cyclooxygenase-2 in the aorta and elevated levels of thromboxane A2 and prostacyclin metabolites in the urine of apoE(-/-) IO.SIGNIFICANCE:
Our results showed that chronic iron overload intensifies the atherosclerotic process and induces endothelial dysfunction in atherosclerotic mice, probably due to the oxidative stress and the imbalance between the relaxing and contractile factors synthesized by the damaged endothelium.Palavras-chave
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Base de dados:
MEDLINE
Assunto principal:
Apolipoproteínas E
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Endotélio Vascular
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Estresse Oxidativo
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Sobrecarga de Ferro
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Aterosclerose
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Hipercolesterolemia
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article