Resveratrol Inhibits Monocytic Cell Chemotaxis to MCP-1 and Prevents Spontaneous Endothelial Cell Migration Through Rho Kinase-Dependent Mechanism

• Published in: Journal of Atherosclerosis and Thrombosis 2011, Vol.18(12), pp.1031-1042
• Main Authors: Cicha, Iwona, Regler, Melanie, Urschel, Katharina, Goppelt-Struebe, Margarete, Daniel, Werner G, Garlichs, Christoph D
• Format: Article
• Language: English
• Subjects: Blotting, Western; Cells, Cultured; Chemokine CCL2 - physiology; Chemotaxis, Leukocyte - drug effects; Dose-Response Relationship, Drug; Endothelial cell migration; Endothelium, Vascular - cytology; Endothelium, Vascular - drug effects; Humans; Monocyte chemotaxis; Monocytes - cytology; Monocytes - drug effects; Phosphorylation; Resveratrol; rho-Associated Kinases - metabolism; RhoA; ROCK inhibition; Stilbenes - pharmacology
• ISSN: 1340-3478; 1880-3873
• DOI: 10.5551/jat.8136

Aim: Inflammatory cell recruitment and intimal neovascularization contribute to atherosclerotic plaque destabilization. The anti-inflammatory red wine polyphenol, resveratrol, has been implicated in cardiovascular protection. In this study, we investigated the effects of resveratrol on endothelial and monocytic cell migration. Methods: Human umbilical vein endothelial cell (EC) migration was assessed in a modified barrier assay. Chemotaxis of THP-1 monocytic cells towards monocyte chemoattractant protein (MCP)-1 was determined using a Boyden chamber. Erk phosphorylation downstream of MCP-1 receptor and activation of myosin phosphatase targeting subunit 1 (pMYPT1) downstream of Rho kinase were determined by Western blotting. Results: In resveratrol-treated cells, progressive shape elongation was observed, evident after 6h of treatment. Treatment with resveratrol (1-20 µmol/L) dose-dependently inhibited EC migration. This effect of resveratrol was independent of nuclear factor (NF)-kappaB and sirtuin 1, but was abrogated in the presence of Rho kinase inhibitors. Moreover, resveratrol induced pMYPT1 activation, indicating a novel mechanism of resveratrol activity in EC. In monocytic cells, treatment with resveratrol significantly inhibited chemotaxis towards MCP-1 already at 1 µmol/L. At a resveratrol concentration of 10 µmol/L, chemotaxis was reduced nearly to the negative control (unstimulated with MCP-1) levels. This effect was independent of NF-kappaB and RhoA signaling. In resveratroltreated monocytic cells, MCP-1-induced Erk phosphorylation downstream of CCR2 receptor was dose-dependently inhibited, as observed by Western blot analysis. Conclusions: Resveratrol dose-dependently inhibited endothelial cell migration and MCP-1-induced monocytic cell chemotaxis. This activity may contribute to the cardioprotective effects of resveratrol by inhibition of intimal neovascularization and monocyte recruitment into the artery wall.