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Grape seed proanthocyanidins attenuate vascular smooth muscle cell proliferation via blocking phosphatidylinositol 3‐kinase‐dependent signaling pathways
Author(s) -
Wang Lang,
Zhu LiHua,
Jiang Hong,
Tang QiZhu,
Yan Ling,
Wang Dong,
Liu Chen,
Bian ZhouYan,
Li Hongliang
Publication year - 2010
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.22080
Subject(s) - nadph oxidase , microbiology and biotechnology , rac1 , reactive oxygen species , vascular smooth muscle , protein kinase b , phosphorylation , signal transduction , p110α , pi3k/akt/mtor pathway , phosphatidylinositol , cell growth , chemistry , biology , biochemistry , endocrinology , smooth muscle
The excess generation of reactive oxygen species (ROS) play important role in the development and progression of diabetes and related vascular complications. Therefore, blocking the production of ROS will be able to improve hyperglycemia‐induced vascular dysfunction. The objective of this study was to determine whether a novel IH636 grape seed proanthocyanidins (GSPs) could protect against hyperproliferation of cultured rat vascular smooth muscle cells (VSMCs) induced by high glucose (HG) and determine the related molecular mechanisms. Our data demonstrated that GSPs markedly inhibited rat VSMCs proliferation as well as ROS generation and NAPDH oxidase activity induced by HG treatment. Further studies revealed that HG treatment resulted in phosphorylation and membrane translocation of Rac1, p47phox, and p67phox subunits leading to NADPH oxidase activation. GSPs treatment remarkably disrupted the phosphorylation and membrane translocation of Rac1, p47phox, and p67phox subunits. More importantly, our data further revealed that GSPs significantly disrupted HG‐induced activation of ERK1/2, JNK1/2, and PI3K/AKT/GSK3β as well as NF‐κB signalings, which were dependent on reactive oxygen species (ROS) generation and Rac1 activation. In addition, our results also demonstrated that HG‐induced cell proliferation and excess ROS production was dependent on the activation of PI3 kinase subunit p110α. Collectively, these results suggest that HG‐induced VSMC growth was attenuated by grape seed proanthocyanidin (GSPs) treatment through blocking PI3 kinase‐dependent signaling pathway, indicating that GSPs may be useful in retarding intimal hyperplasia and restenosis in diabetic vessels. J. Cell. Physiol. 223:713–726, 2010. © 2010 Wiley‐Liss, Inc.