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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2003;23:1001.)
© 2003 American Heart Association, Inc.

Vascular Biology

Red Wine Polyphenolic Compounds Inhibit Vascular Endothelial Growth Factor Expression in Vascular Smooth Muscle Cells by Preventing the Activation of the p38 Mitogen-Activated Protein Kinase Pathway

Min-Ho Oak; Marta Chataigneau; Thérèse Keravis; Thierry Chataigneau; Alain Beretz; Ramaroson Andriantsitohaina; Jean-Claude Stoclet; Soon-Jae Chang; Valérie B. Schini-Kerth

From Pharmacologie et Physico-Chimie des Interactions Cellulaires et Moléculaires, UMR CNRS 7034 (M.-H.O., M.C., T.K., T.C., A.B., R.A., J.-C.S., V.B.S.-K.), Université Louis Pasteur de Strasbourg, France, and Research and Development Center, Yangji Chemicals (S.-J.C.), An-San, South Korea.

Correspondence to Valérie B. Schini-Kerth, PhD, UMR CNRS 7034, Université Louis Pasteur de Strasbourg, Faculté de Pharmacie, 74, route du Rhin, B.P. 24, F-67401 Illkirch, France. E-mail schini{at}aspirine.u-strasbg.fr

Objective— Moderate consumption of red wine has a beneficial effect on the cardiovascular system. This study examines whether red wine polyphenolic compounds (RWPCs) affect vascular endothelial growth factor (VEGF) expression, a major angiogenic and proatherosclerotic factor in vascular smooth muscle cells (VSMCs).

Methods and Results— VEGF mRNA expression was assessed by Northern blot analysis and the release of VEGF by immunoassay in cultured VSMCs. Short-term and long-term exposure of VSMCs to RWPCs inhibited VEGF mRNA expression and release of VEGF in response to platelet-derived growth factor AB (PDGF_AB), transforming growth factor-ß₁, or thrombin. The PDGF_AB-induced expression of VEGF was markedly reduced by SB203580 (inhibitor of p38 mitogen-activated protein kinase [MAPK]), antioxidants, and diphenylene iodonium (inhibitor of flavin-dependent enzymes), slightly reduced by PD98059 (inhibitor of MEK), and not significantly affected by wortmannin (inhibitor of PI-3-kinase) and L-JNKI (inhibitor of JNK). Short-term and long-term treatment of VSMCs with RWPCs markedly reduced PDGF_AB-induced production of reactive oxygen species and phosphorylation of p38 MAPK.

Conclusions— These data indicate that RWPCs strongly inhibit growth factor–induced VEGF expression in VSMCs by preventing the redox-sensitive activation of the p38 MAPK pathway. The potential antiangiogenic and antiatherosclerotic properties of RWPCs are likely to contribute to cardiovascular protection by preventing the development of atherosclerotic lesions.

Key Words: red wine polyphenolic compounds • vascular endothelial growth factor • vascular smooth muscle cells • atherosclerosis • angiogenesis

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