PT  - JOURNAL ARTICLE
AU  - Jianhui, Zhuang
AU  - Wenhui, Peng
AU  - Hailing, Li
AU  - Yuyan, Lu
AU  - Ke, Wang
AU  - Ying, Li
AU  - Fan, Fan
AU  - Yawei, Xu
TI  - ASSA13-03-13 Inhibitory Effects of Vinpocetine on the Progression of Atherosclerosis Are Mediated by Akt/NF-kB Dependent Mechanisms
AID  - 10.1136/heartjnl-2013-303992.053
DP  - 2013 Apr 01
TA  - Heart
PG  - A18--A18
VI  - 99
IP  - Suppl 1
4099  - http://heart.bmj.com/content/99/Suppl_1/A18.1.short
4100  - http://heart.bmj.com/content/99/Suppl_1/A18.1.full
SO  - Heart2013 Apr 01; 99
AB  - Objective Recent studies have found additional role 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. Methods and Results 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 the expression of TNF-alpha and matrix metalloproteinase-9 (MMP-9) within plaque area. In vitro experiments exhibited a significant decrease in monocyte adhension treated with vinpocetine. In parallel with few changes in ox-LDL uptake and foam cell formation, the expression levels of scavenger receptor A and CD 36 were not altered after treatment with vinpocetine. Further, active TNF-alpha, IL-6, monocyte chemoattractant protein-1 and MMP-9 expression induced by ox-LDL was 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 restored the enhanced Akt, IKK-alpha/beta, IkappaB-alpha phosphorylation and NF-kappaB activity induced by ox-LDL. Cotreatment with LY294002, a specific Akt inhibitor, augmented the inhibitory effects of vinpocetine on IKK-alpha/beta and IkappaB-alpha phosphorylation, suggesting that inhibition of NF-kappaB activity was partly caused by Akt dephosphorylation. Knockdown of PDE1B resulted in an increase of intracellular cGMP contents, however, did not affect Akt, IKK-alpha/beta and IkappaB-alpha phosphorylation. Conclusions Vinpocetine exerts anti-atherogenic effects through inhibition of monocyte adhension, oxidative stress and inflammatory response, which are mediated by Akt/NF-kappaB dependent pathway but independent of PDE1 blockade in macrophages.