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Resveratrol inhibits monocytic cell chemotaxis to MCP-1 and prevents spontaneous endothelial cell migration through Rho kinase-dependent mechanism
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نویسنده
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cicha i. ,regler m. ,urschel k. ,goppelt-struebe m. ,daniel w.g. ,garlichs c.d.
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منبع
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journal of atherosclerosis and thrombosis - 2011 - دوره : 18 - شماره : 12 - صفحه:1031 -1042
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چکیده
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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.
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کلیدواژه
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Endothelial cell migration; Monocyte chemotaxis; Resveratrol; RhoA; ROCK inhibition
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آدرس
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department of cardiology and angiology,university of erlangen-nuremberg,erlangen, Germany, department of cardiology and angiology,university of erlangen-nuremberg,erlangen, Germany, department of cardiology and angiology,university of erlangen-nuremberg,erlangen, Germany, department of nephrology and hypertension,university of erlangen-nuremberg,erlangen, Germany, department of cardiology and angiology,university of erlangen-nuremberg,erlangen, Germany, department of cardiology and angiology,university of erlangen-nuremberg,erlangen, Germany
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Authors
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