Grape seed proanthocyanidins attenuate vascular smooth muscle cell proliferation via blocking phosphatidylinositol 3-kinase-dependent signaling pathways

Lang Wang, Li Hua Zhu, Hong Jiang, Qi Zhu Tang, Ling Yan, Dong Wang, Chen Liu, Zhou Yan Bian, Hongliang Li

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

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/GSK3b as well as NF-kB 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 p110a. 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.

Original languageEnglish (US)
Pages (from-to)713-726
Number of pages14
JournalJournal of Cellular Physiology
Volume223
Issue number3
DOIs
StatePublished - Jun 1 2010

Fingerprint

Phosphatidylinositol 3-Kinase
Cell proliferation
Vascular Smooth Muscle
Smooth Muscle Myocytes
Muscle
Cell Proliferation
Reactive Oxygen Species
Glucose
Chemical activation
Phosphatidylinositol 3-Kinases
Phosphorylation
Blood Vessels
Rats
Tunica Intima
Membranes
NF-kappa B
NADPH Oxidase
Cell growth
Diabetes Complications
Medical problems

All Science Journal Classification (ASJC) codes

  • Physiology
  • Clinical Biochemistry
  • Cell Biology

Cite this

Grape seed proanthocyanidins attenuate vascular smooth muscle cell proliferation via blocking phosphatidylinositol 3-kinase-dependent signaling pathways. / Wang, Lang; Zhu, Li Hua; Jiang, Hong; Tang, Qi Zhu; Yan, Ling; Wang, Dong; Liu, Chen; Bian, Zhou Yan; Li, Hongliang.

In: Journal of Cellular Physiology, Vol. 223, No. 3, 01.06.2010, p. 713-726.

Research output: Contribution to journalArticle

Wang, Lang ; Zhu, Li Hua ; Jiang, Hong ; Tang, Qi Zhu ; Yan, Ling ; Wang, Dong ; Liu, Chen ; Bian, Zhou Yan ; Li, Hongliang. / Grape seed proanthocyanidins attenuate vascular smooth muscle cell proliferation via blocking phosphatidylinositol 3-kinase-dependent signaling pathways. In: Journal of Cellular Physiology. 2010 ; Vol. 223, No. 3. pp. 713-726.
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