Cargando…

Genistein alleviates chronic vascular inflammatory response via the miR-21/NF-κB p65 axis in lipopolysaccharide-treated mice

Chronic vascular inflammatory response is an important pathological basis of cardiovascular disease. Genistein (GEN), a natural compound, exhibits anti-inflammatory effects. The aim of the present study was to investigate the effects of GEN on lipopolysaccharide (LPS)-induced chronic vascular inflam...

Descripción completa

Detalles Bibliográficos
Autores principales: Xie, Xiaolin, Cong, Li, Liu, Sujuan, Xiang, Liping, Fu, Xiaohua
Formato: Online Artículo Texto
Lenguaje:English
Publicado: D.A. Spandidos 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7809901/
https://www.ncbi.nlm.nih.gov/pubmed/33495831
http://dx.doi.org/10.3892/mmr.2021.11831
_version_ 1783637210143129600
author Xie, Xiaolin
Cong, Li
Liu, Sujuan
Xiang, Liping
Fu, Xiaohua
author_facet Xie, Xiaolin
Cong, Li
Liu, Sujuan
Xiang, Liping
Fu, Xiaohua
author_sort Xie, Xiaolin
collection PubMed
description Chronic vascular inflammatory response is an important pathological basis of cardiovascular disease. Genistein (GEN), a natural compound, exhibits anti-inflammatory effects. The aim of the present study was to investigate the effects of GEN on lipopolysaccharide (LPS)-induced chronic vascular inflammatory response in mice and explore the underlying anti-inflammatory mechanisms. C57BL/6 mice were fed with a high-fat diet combined with intraperitoneal injection of LPS to induce chronic vascular inflammation. The expression levels of TNF-α, IL-6 and microRNA (miR)-21 in the vasculature were detected via reverse transcription-quantitative (RT-q)PCR. The protein levels of inducible nitric oxide synthase (iNOS) and NF-κB p65 were detected via western blotting. NF-κB p65 was also analyzed via immunohistochemistry and immunofluorescence (IF). In addition, after transfection with miR-21 mimic or inhibitor for 24 h, vascular endothelial cells (VECs) were treated with GEN and LPS. RT-qPCR and western blot analyses were performed to detect the expression of TNF-α, IL-6, miR-21 and iNOS, and the protein levels of iNOS and NF-κB p65, respectively. IF was used to measure NF-κB p65 nuclear translocation. The results revealed that GEN significantly decreased the expression of inflammation-associated vascular factors in LPS-treated C57BL/6 mice, including TNF-α, IL-6, iNOS, NF-κB p65 and miR-21. Furthermore, miR-21 antagomir enhanced the anti-inflammatory effects of GEN. In LPS-induced VECs, miR-21 mimic increased inflammation-associated factor expression and attenuated the anti-inflammatory effects of GEN, whereas miR-21 inhibitor induced opposing effects. Therefore, the results of the present study suggested that GEN inhibited chronic vascular inflammatory response in mice, which may be associated with the inhibition of VEC inflammatory injury via the miR-21/NF-κB p65 pathway.
format Online
Article
Text
id pubmed-7809901
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher D.A. Spandidos
record_format MEDLINE/PubMed
spelling pubmed-78099012021-01-21 Genistein alleviates chronic vascular inflammatory response via the miR-21/NF-κB p65 axis in lipopolysaccharide-treated mice Xie, Xiaolin Cong, Li Liu, Sujuan Xiang, Liping Fu, Xiaohua Mol Med Rep Articles Chronic vascular inflammatory response is an important pathological basis of cardiovascular disease. Genistein (GEN), a natural compound, exhibits anti-inflammatory effects. The aim of the present study was to investigate the effects of GEN on lipopolysaccharide (LPS)-induced chronic vascular inflammatory response in mice and explore the underlying anti-inflammatory mechanisms. C57BL/6 mice were fed with a high-fat diet combined with intraperitoneal injection of LPS to induce chronic vascular inflammation. The expression levels of TNF-α, IL-6 and microRNA (miR)-21 in the vasculature were detected via reverse transcription-quantitative (RT-q)PCR. The protein levels of inducible nitric oxide synthase (iNOS) and NF-κB p65 were detected via western blotting. NF-κB p65 was also analyzed via immunohistochemistry and immunofluorescence (IF). In addition, after transfection with miR-21 mimic or inhibitor for 24 h, vascular endothelial cells (VECs) were treated with GEN and LPS. RT-qPCR and western blot analyses were performed to detect the expression of TNF-α, IL-6, miR-21 and iNOS, and the protein levels of iNOS and NF-κB p65, respectively. IF was used to measure NF-κB p65 nuclear translocation. The results revealed that GEN significantly decreased the expression of inflammation-associated vascular factors in LPS-treated C57BL/6 mice, including TNF-α, IL-6, iNOS, NF-κB p65 and miR-21. Furthermore, miR-21 antagomir enhanced the anti-inflammatory effects of GEN. In LPS-induced VECs, miR-21 mimic increased inflammation-associated factor expression and attenuated the anti-inflammatory effects of GEN, whereas miR-21 inhibitor induced opposing effects. Therefore, the results of the present study suggested that GEN inhibited chronic vascular inflammatory response in mice, which may be associated with the inhibition of VEC inflammatory injury via the miR-21/NF-κB p65 pathway. D.A. Spandidos 2021-03 2021-01-07 /pmc/articles/PMC7809901/ /pubmed/33495831 http://dx.doi.org/10.3892/mmr.2021.11831 Text en Copyright: © Xie 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
Xie, Xiaolin
Cong, Li
Liu, Sujuan
Xiang, Liping
Fu, Xiaohua
Genistein alleviates chronic vascular inflammatory response via the miR-21/NF-κB p65 axis in lipopolysaccharide-treated mice
title Genistein alleviates chronic vascular inflammatory response via the miR-21/NF-κB p65 axis in lipopolysaccharide-treated mice
title_full Genistein alleviates chronic vascular inflammatory response via the miR-21/NF-κB p65 axis in lipopolysaccharide-treated mice
title_fullStr Genistein alleviates chronic vascular inflammatory response via the miR-21/NF-κB p65 axis in lipopolysaccharide-treated mice
title_full_unstemmed Genistein alleviates chronic vascular inflammatory response via the miR-21/NF-κB p65 axis in lipopolysaccharide-treated mice
title_short Genistein alleviates chronic vascular inflammatory response via the miR-21/NF-κB p65 axis in lipopolysaccharide-treated mice
title_sort genistein alleviates chronic vascular inflammatory response via the mir-21/nf-κb p65 axis in lipopolysaccharide-treated mice
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7809901/
https://www.ncbi.nlm.nih.gov/pubmed/33495831
http://dx.doi.org/10.3892/mmr.2021.11831
work_keys_str_mv AT xiexiaolin genisteinalleviateschronicvascularinflammatoryresponseviathemir21nfkbp65axisinlipopolysaccharidetreatedmice
AT congli genisteinalleviateschronicvascularinflammatoryresponseviathemir21nfkbp65axisinlipopolysaccharidetreatedmice
AT liusujuan genisteinalleviateschronicvascularinflammatoryresponseviathemir21nfkbp65axisinlipopolysaccharidetreatedmice
AT xiangliping genisteinalleviateschronicvascularinflammatoryresponseviathemir21nfkbp65axisinlipopolysaccharidetreatedmice
AT fuxiaohua genisteinalleviateschronicvascularinflammatoryresponseviathemir21nfkbp65axisinlipopolysaccharidetreatedmice