Exendin4 reverses endothelial dysfunction in mice fed a highcholesterol diet by a GTP cyclohydrolase1/tetrahydrobiopterin pathway.
Mol Med Rep
; 18(3): 3350-3358, 2018 Sep.
Article
em En
| MEDLINE
| ID: mdl-30085331
ABSTRACT
The present study examined whether exendin4 (Ex4) can improve the endothelial dysfunction of apolipoprotein E knockout (APOEKO) mice fed a highcholesterol diet and the potential mechanism by which it acts. Genetically wildtype (WT) C57BL/6 mice and APOEKO mice of C57BL/6 background, were each randomly assigned to receive either Ex4 treatment (Ex4treated, for 8 weeks) or not (control). The 4 groups were fed the same highcholesterol diet for 8 weeks. The following were measured at the end of the eighth week Endotheliumdependent vasodilation of the arteries; plasma nitric oxide (NO) and metabolic index; levels of endothelial NO synthase (eNOS); phosphorylated eNOS (peNOS; Ser1,177); guanosine triphosphate cyclohydrolase1 (GCH1); and tetrahydrobiopterin (THB). Ex4 treatment was associated with higher peNOS levels in the WT group and in the APOEKO group, and higher vascular expression of GCH1 and higher arterial THB content, compared with baseline values. The results of the present study suggested that Ex4 may exert cardioprotective effects by reversing highcholesterol dietinduced endothelial dysfunction in APOEKO mice. The protective mechanism is probably associated with the promotion of the expression levels of GCH1 protein and THB that maintain the normal function of eNOS.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Apolipoproteínas E
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Peptídeos
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Peçonhas
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Endotélio Vascular
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Receptor do Peptídeo Semelhante ao Glucagon 1
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Hipoglicemiantes
Limite:
Animals
Idioma:
En
Revista:
Mol Med Rep
Ano de publicação:
2018
Tipo de documento:
Article