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Exendin-4 reverses endothelial dysfunction in mice fed a high-cholesterol diet by a GTP cyclohydrolase-1/tetrahydrobiopterin pathway

The present study examined whether exendin-4 (Ex4) can improve the endothelial dysfunction of apolipoprotein E knockout (APOE-KO) mice fed a high-cholesterol diet and the potential mechanism by which it acts. Genetically wild-type (WT) C57BL/6 mice and APOE-KO mice of C57BL/6 background, were each r...

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Autores principales: Tang, Zhiqi, Liu, Lijuan, Guo, Yujie, Deng, Guoxiong, Chen, Meixiang, Wei, Jinru
Formato: Online Artículo Texto
Lenguaje:English
Publicado: D.A. Spandidos 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6102738/
https://www.ncbi.nlm.nih.gov/pubmed/30085331
http://dx.doi.org/10.3892/mmr.2018.9345
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author Tang, Zhiqi
Liu, Lijuan
Guo, Yujie
Deng, Guoxiong
Chen, Meixiang
Wei, Jinru
author_facet Tang, Zhiqi
Liu, Lijuan
Guo, Yujie
Deng, Guoxiong
Chen, Meixiang
Wei, Jinru
author_sort Tang, Zhiqi
collection PubMed
description The present study examined whether exendin-4 (Ex4) can improve the endothelial dysfunction of apolipoprotein E knockout (APOE-KO) mice fed a high-cholesterol diet and the potential mechanism by which it acts. Genetically wild-type (WT) C57BL/6 mice and APOE-KO mice of C57BL/6 background, were each randomly assigned to receive either Ex4 treatment (Ex4-treated, for 8 weeks) or not (control). The 4 groups were fed the same high-cholesterol diet for 8 weeks. The following were measured at the end of the eighth week: Endothelium-dependent vasodilation of the arteries; plasma nitric oxide (NO) and metabolic index; levels of endothelial NO synthase (eNOS); phosphorylated eNOS (p-eNOS; Ser-1,177); guanosine triphosphate cyclohydrolase-1 (GCH1); and tetrahydrobiopterin (THB). Ex4 treatment was associated with higher p-eNOS levels in the WT group and in the APOE-KO 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 high-cholesterol diet-induced endothelial dysfunction in APOE-KO 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.
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spelling pubmed-61027382018-08-23 Exendin-4 reverses endothelial dysfunction in mice fed a high-cholesterol diet by a GTP cyclohydrolase-1/tetrahydrobiopterin pathway Tang, Zhiqi Liu, Lijuan Guo, Yujie Deng, Guoxiong Chen, Meixiang Wei, Jinru Mol Med Rep Articles The present study examined whether exendin-4 (Ex4) can improve the endothelial dysfunction of apolipoprotein E knockout (APOE-KO) mice fed a high-cholesterol diet and the potential mechanism by which it acts. Genetically wild-type (WT) C57BL/6 mice and APOE-KO mice of C57BL/6 background, were each randomly assigned to receive either Ex4 treatment (Ex4-treated, for 8 weeks) or not (control). The 4 groups were fed the same high-cholesterol diet for 8 weeks. The following were measured at the end of the eighth week: Endothelium-dependent vasodilation of the arteries; plasma nitric oxide (NO) and metabolic index; levels of endothelial NO synthase (eNOS); phosphorylated eNOS (p-eNOS; Ser-1,177); guanosine triphosphate cyclohydrolase-1 (GCH1); and tetrahydrobiopterin (THB). Ex4 treatment was associated with higher p-eNOS levels in the WT group and in the APOE-KO 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 high-cholesterol diet-induced endothelial dysfunction in APOE-KO 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. D.A. Spandidos 2018-09 2018-08-01 /pmc/articles/PMC6102738/ /pubmed/30085331 http://dx.doi.org/10.3892/mmr.2018.9345 Text en Copyright: © Tang et al. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
spellingShingle Articles
Tang, Zhiqi
Liu, Lijuan
Guo, Yujie
Deng, Guoxiong
Chen, Meixiang
Wei, Jinru
Exendin-4 reverses endothelial dysfunction in mice fed a high-cholesterol diet by a GTP cyclohydrolase-1/tetrahydrobiopterin pathway
title Exendin-4 reverses endothelial dysfunction in mice fed a high-cholesterol diet by a GTP cyclohydrolase-1/tetrahydrobiopterin pathway
title_full Exendin-4 reverses endothelial dysfunction in mice fed a high-cholesterol diet by a GTP cyclohydrolase-1/tetrahydrobiopterin pathway
title_fullStr Exendin-4 reverses endothelial dysfunction in mice fed a high-cholesterol diet by a GTP cyclohydrolase-1/tetrahydrobiopterin pathway
title_full_unstemmed Exendin-4 reverses endothelial dysfunction in mice fed a high-cholesterol diet by a GTP cyclohydrolase-1/tetrahydrobiopterin pathway
title_short Exendin-4 reverses endothelial dysfunction in mice fed a high-cholesterol diet by a GTP cyclohydrolase-1/tetrahydrobiopterin pathway
title_sort exendin-4 reverses endothelial dysfunction in mice fed a high-cholesterol diet by a gtp cyclohydrolase-1/tetrahydrobiopterin pathway
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6102738/
https://www.ncbi.nlm.nih.gov/pubmed/30085331
http://dx.doi.org/10.3892/mmr.2018.9345
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