期刊
PLOS ONE
卷 8, 期 12, 页码 -出版社
PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pone.0082509
关键词
-
资金
- National Natural Science Foundation of China [30900520, 81070107]
- Shanghai Rising-Star Program [10QA1405500]
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-alpha, 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, IKK alpha/beta, I kappa B alpha phosphorylation and NF-kappa B activity induced by ox-LDL, and the inhibition of NF-kappa B activity was partly caused by Akt dephosphorylation. However, knockdown of PDE1B did not affect Akt, IKK alpha/beta and I kappa B alpha 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-kappa B dependent pathway but independent of PDE1 blockade in macrophages.
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