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Inhibitory Effects of Vinpocetine on the Progression of Atherosclerosis Are Mediated by Akt/NF-κB Dependent Mechanisms in apoE(-/-) Mice

BACKGROUND: 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 p...

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Autores principales: Zhuang, Jianhui, Peng, Wenhui, Li, Hailing, Lu, Yuyan, Wang, Ke, Fan, Fan, Li, Shuang, Xu, Yawei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3857260/
https://www.ncbi.nlm.nih.gov/pubmed/24349299
http://dx.doi.org/10.1371/journal.pone.0082509
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author Zhuang, Jianhui
Peng, Wenhui
Li, Hailing
Lu, Yuyan
Wang, Ke
Fan, Fan
Li, Shuang
Xu, Yawei
author_facet Zhuang, Jianhui
Peng, Wenhui
Li, Hailing
Lu, Yuyan
Wang, Ke
Fan, Fan
Li, Shuang
Xu, Yawei
author_sort Zhuang, Jianhui
collection PubMed
description BACKGROUND: 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. METHODOLOGY/PRINCIPAL FINDINGS: 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-1and 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. CONCLUSIONS: 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.
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spelling pubmed-38572602013-12-13 Inhibitory Effects of Vinpocetine on the Progression of Atherosclerosis Are Mediated by Akt/NF-κB Dependent Mechanisms in apoE(-/-) Mice Zhuang, Jianhui Peng, Wenhui Li, Hailing Lu, Yuyan Wang, Ke Fan, Fan Li, Shuang Xu, Yawei PLoS One Research Article BACKGROUND: 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. METHODOLOGY/PRINCIPAL FINDINGS: 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-1and 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. CONCLUSIONS: 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. Public Library of Science 2013-12-09 /pmc/articles/PMC3857260/ /pubmed/24349299 http://dx.doi.org/10.1371/journal.pone.0082509 Text en © 2013 Zhuang et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Zhuang, Jianhui
Peng, Wenhui
Li, Hailing
Lu, Yuyan
Wang, Ke
Fan, Fan
Li, Shuang
Xu, Yawei
Inhibitory Effects of Vinpocetine on the Progression of Atherosclerosis Are Mediated by Akt/NF-κB Dependent Mechanisms in apoE(-/-) Mice
title 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_short 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
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3857260/
https://www.ncbi.nlm.nih.gov/pubmed/24349299
http://dx.doi.org/10.1371/journal.pone.0082509
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