Soluble Epoxide Hydrolase Inhibition Protected against Angiotensin II-induced Adventitial Remodeling

Abstract Epoxyeicosatrienoic acids (EETs), the metabolites of cytochrome P450 epoxygenases derived from arachidonic acid, exert important biological activities in maintaining cardiovascular homeostasis. Soluble epoxide hydrolase (sEH) hydrolyzes EETs to less biologically active dihydroxyeicosatrieno...

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Autores principales:	Chi Zhou, Jin Huang, Qing Li, Jiali Nie, Xizhen Xu, Dao Wen Wang
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/6fbfcd131c4f4af2950194eff592a1e4
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spelling	oai:doaj.org-article:6fbfcd131c4f4af2950194eff592a1e42021-12-02T16:06:45ZSoluble Epoxide Hydrolase Inhibition Protected against Angiotensin II-induced Adventitial Remodeling10.1038/s41598-017-07512-12045-2322https://doaj.org/article/6fbfcd131c4f4af2950194eff592a1e42017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-07512-1https://doaj.org/toc/2045-2322Abstract Epoxyeicosatrienoic acids (EETs), the metabolites of cytochrome P450 epoxygenases derived from arachidonic acid, exert important biological activities in maintaining cardiovascular homeostasis. Soluble epoxide hydrolase (sEH) hydrolyzes EETs to less biologically active dihydroxyeicosatrienoic acids. However, the effects of sEH inhibition on adventitial remodeling remain inconclusive. In this study, the adventitial remodeling model was established by continuous Ang II infusion for 2 weeks in C57BL/6 J mice, before which sEH inhibitor 1-trifluoromethoxyphenyl-3-(1-propionylpiperidin-4-yl) urea (TPPU) was administered by gavage. Adventitial remodeling was evaluated by histological analysis, western blot, immunofluorescent staining, calcium imaging, CCK-8 and transwell assay. Results showed that Ang II infusion significantly induced vessel wall thickening, collagen deposition, and overexpression of α-SMA and PCNA in aortic adventitia, respectively. Interestingly, these injuries were attenuated by TPPU administration. Additionally, TPPU pretreatment overtly prevented Ang II-induced primary adventitial fibroblasts activation, characterized by differentiation, proliferation, migration, and collagen synthesis via Ca2+-calcineurin/NFATc3 signaling pathway in vitro. In summary, our results suggest that inhibition of sEH could be considered as a novel therapeutic strategy to treat adventitial remodeling related disorders.Chi ZhouJin HuangQing LiJiali NieXizhen XuDao Wen WangNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-9 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Chi Zhou Jin Huang Qing Li Jiali Nie Xizhen Xu Dao Wen Wang Soluble Epoxide Hydrolase Inhibition Protected against Angiotensin II-induced Adventitial Remodeling
description	Abstract Epoxyeicosatrienoic acids (EETs), the metabolites of cytochrome P450 epoxygenases derived from arachidonic acid, exert important biological activities in maintaining cardiovascular homeostasis. Soluble epoxide hydrolase (sEH) hydrolyzes EETs to less biologically active dihydroxyeicosatrienoic acids. However, the effects of sEH inhibition on adventitial remodeling remain inconclusive. In this study, the adventitial remodeling model was established by continuous Ang II infusion for 2 weeks in C57BL/6 J mice, before which sEH inhibitor 1-trifluoromethoxyphenyl-3-(1-propionylpiperidin-4-yl) urea (TPPU) was administered by gavage. Adventitial remodeling was evaluated by histological analysis, western blot, immunofluorescent staining, calcium imaging, CCK-8 and transwell assay. Results showed that Ang II infusion significantly induced vessel wall thickening, collagen deposition, and overexpression of α-SMA and PCNA in aortic adventitia, respectively. Interestingly, these injuries were attenuated by TPPU administration. Additionally, TPPU pretreatment overtly prevented Ang II-induced primary adventitial fibroblasts activation, characterized by differentiation, proliferation, migration, and collagen synthesis via Ca2+-calcineurin/NFATc3 signaling pathway in vitro. In summary, our results suggest that inhibition of sEH could be considered as a novel therapeutic strategy to treat adventitial remodeling related disorders.
format	article
author	Chi Zhou Jin Huang Qing Li Jiali Nie Xizhen Xu Dao Wen Wang
author_facet	Chi Zhou Jin Huang Qing Li Jiali Nie Xizhen Xu Dao Wen Wang
author_sort	Chi Zhou
title	Soluble Epoxide Hydrolase Inhibition Protected against Angiotensin II-induced Adventitial Remodeling
title_short	Soluble Epoxide Hydrolase Inhibition Protected against Angiotensin II-induced Adventitial Remodeling
title_full	Soluble Epoxide Hydrolase Inhibition Protected against Angiotensin II-induced Adventitial Remodeling
title_fullStr	Soluble Epoxide Hydrolase Inhibition Protected against Angiotensin II-induced Adventitial Remodeling
title_full_unstemmed	Soluble Epoxide Hydrolase Inhibition Protected against Angiotensin II-induced Adventitial Remodeling
title_sort	soluble epoxide hydrolase inhibition protected against angiotensin ii-induced adventitial remodeling
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/6fbfcd131c4f4af2950194eff592a1e4
work_keys_str_mv	AT chizhou solubleepoxidehydrolaseinhibitionprotectedagainstangiotensiniiinducedadventitialremodeling AT jinhuang solubleepoxidehydrolaseinhibitionprotectedagainstangiotensiniiinducedadventitialremodeling AT qingli solubleepoxidehydrolaseinhibitionprotectedagainstangiotensiniiinducedadventitialremodeling AT jialinie solubleepoxidehydrolaseinhibitionprotectedagainstangiotensiniiinducedadventitialremodeling AT xizhenxu solubleepoxidehydrolaseinhibitionprotectedagainstangiotensiniiinducedadventitialremodeling AT daowenwang solubleepoxidehydrolaseinhibitionprotectedagainstangiotensiniiinducedadventitialremodeling
_version_	1718384846306279424

Soluble Epoxide Hydrolase Inhibition Protected against Angiotensin II-induced Adventitial Remodeling

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