Inhibitory effects of vinpocetine on the progression of atherosclerosis are mediated by Akt/NF-κB dependent mechanisms in apoE-/- mice.

<h4>Background</h4>Recent studies have found additional roles for vinpocetine, a potent phosphodiesterase type I inhibitor, in anti-proliferation and anti-inflammation of vascular smooth muscle cells and cancer cells via different mechanisms. In this study, we attempted to investigate wh...

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Autores principales:	Jianhui Zhuang, Wenhui Peng, Hailing Li, Yuyan Lu, Ke Wang, Fan Fan, Shuang Li, Yawei Xu
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/53599c8a526c4443a74b48e122e108aa
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spelling	oai:doaj.org-article:53599c8a526c4443a74b48e122e108aa2021-11-18T08:42:52ZInhibitory effects of vinpocetine on the progression of atherosclerosis are mediated by Akt/NF-κB dependent mechanisms in apoE-/- mice.1932-620310.1371/journal.pone.0082509https://doaj.org/article/53599c8a526c4443a74b48e122e108aa2013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24349299/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>Recent studies have found additional roles for vinpocetine, a potent phosphodiesterase type I inhibitor, in anti-proliferation and anti-inflammation of vascular smooth muscle cells and cancer cells via different mechanisms. In this study, we attempted to investigate whether vinpocetine protected against atherosclerotic development in apoE(-/-) mice and explore the underlying anti-atherogenic mechanisms in macrophages.<h4>Methodology/principal findings</h4>Vinpocetine markedly decreased atherosclerotic lesion size in apoE(-/-) mice measured by oil red O. Masson's trichrome staining and immunohistochemical analyses revealed that vinpocetine significantly increased the thickness of fibrous cap, reduced the size of lipid-rich necrotic core and attenuated inflammation. In vitro experiments exhibited a significant decrease in monocyte adhesion treated with vinpocetine. Further, active TNF-α, IL-6, monocyte chemoattractant protein-1 and matrix metalloproteinase-9 expression induced by ox-LDL were attenuated by vinpocetine in a dose-dependent manner. Similarly, ox-LDL-induced reactive oxygen species were significantly repressed by vinpocetine. Both western blot and luciferase activity assay showed that vinpocetine inhibited the enhanced Akt, IKKα/β, IκBα phosphorylation and NF-κB activity induced by ox-LDL, and the inhibition of NF-κB activity was partly caused by Akt dephosphorylation. However, knockdown of PDE1B did not affect Akt, IKKα/β and IκBα phosphorylation.<h4>Conclusions</h4>These results suggest that vinpocetine exerts anti-atherogenic effects through inhibition of monocyte adhesion, oxidative stress and inflammatory response, which are mediated by Akt/NF-κB dependent pathway but independent of PDE1 blockade in macrophages.Jianhui ZhuangWenhui PengHailing LiYuyan LuKe WangFan FanShuang LiYawei XuPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 12, p e82509 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Jianhui Zhuang Wenhui Peng Hailing Li Yuyan Lu Ke Wang Fan Fan Shuang Li Yawei Xu Inhibitory effects of vinpocetine on the progression of atherosclerosis are mediated by Akt/NF-κB dependent mechanisms in apoE-/- mice.
description	<h4>Background</h4>Recent studies have found additional roles for vinpocetine, a potent phosphodiesterase type I inhibitor, in anti-proliferation and anti-inflammation of vascular smooth muscle cells and cancer cells via different mechanisms. In this study, we attempted to investigate whether vinpocetine protected against atherosclerotic development in apoE(-/-) mice and explore the underlying anti-atherogenic mechanisms in macrophages.<h4>Methodology/principal findings</h4>Vinpocetine markedly decreased atherosclerotic lesion size in apoE(-/-) mice measured by oil red O. Masson's trichrome staining and immunohistochemical analyses revealed that vinpocetine significantly increased the thickness of fibrous cap, reduced the size of lipid-rich necrotic core and attenuated inflammation. In vitro experiments exhibited a significant decrease in monocyte adhesion treated with vinpocetine. Further, active TNF-α, IL-6, monocyte chemoattractant protein-1 and matrix metalloproteinase-9 expression induced by ox-LDL were attenuated by vinpocetine in a dose-dependent manner. Similarly, ox-LDL-induced reactive oxygen species were significantly repressed by vinpocetine. Both western blot and luciferase activity assay showed that vinpocetine inhibited the enhanced Akt, IKKα/β, IκBα phosphorylation and NF-κB activity induced by ox-LDL, and the inhibition of NF-κB activity was partly caused by Akt dephosphorylation. However, knockdown of PDE1B did not affect Akt, IKKα/β and IκBα phosphorylation.<h4>Conclusions</h4>These results suggest that vinpocetine exerts anti-atherogenic effects through inhibition of monocyte adhesion, oxidative stress and inflammatory response, which are mediated by Akt/NF-κB dependent pathway but independent of PDE1 blockade in macrophages.
format	article
author	Jianhui Zhuang Wenhui Peng Hailing Li Yuyan Lu Ke Wang Fan Fan Shuang Li Yawei Xu
author_facet	Jianhui Zhuang Wenhui Peng Hailing Li Yuyan Lu Ke Wang Fan Fan Shuang Li Yawei Xu
author_sort	Jianhui Zhuang
title	Inhibitory effects of vinpocetine on the progression of atherosclerosis are mediated by Akt/NF-κB dependent mechanisms in apoE-/- mice.
title_short	Inhibitory effects of vinpocetine on the progression of atherosclerosis are mediated by Akt/NF-κB dependent mechanisms in apoE-/- mice.
title_full	Inhibitory effects of vinpocetine on the progression of atherosclerosis are mediated by Akt/NF-κB dependent mechanisms in apoE-/- mice.
title_fullStr	Inhibitory effects of vinpocetine on the progression of atherosclerosis are mediated by Akt/NF-κB dependent mechanisms in apoE-/- mice.
title_full_unstemmed	Inhibitory effects of vinpocetine on the progression of atherosclerosis are mediated by Akt/NF-κB dependent mechanisms in apoE-/- mice.
title_sort	inhibitory effects of vinpocetine on the progression of atherosclerosis are mediated by akt/nf-κb dependent mechanisms in apoe-/- mice.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/53599c8a526c4443a74b48e122e108aa
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Inhibitory effects of vinpocetine on the progression of atherosclerosis are mediated by Akt/NF-κB dependent mechanisms in apoE-/- mice.

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