Resveratrol, a Polyphenolic Phytostilbene, Inhibits Endothelial Monocyte Chemotactic Protein-1 Synthesis and Secretion (original) (raw)
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Research Articles| December 21 2006
aDepartment of Surgery, University of Rochester Medical Center, Rochester, N.Y., and
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aDepartment of Surgery, University of Rochester Medical Center, Rochester, N.Y., and
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aDepartment of Surgery, University of Rochester Medical Center, Rochester, N.Y., and
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aDepartment of Surgery, University of Rochester Medical Center, Rochester, N.Y., and
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aDepartment of Surgery, University of Rochester Medical Center, Rochester, N.Y., and
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bDepartment of Surgery, Indiana University School of Medicine, Indianapolis, Ind., USA;
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cVascular Health Research Centre, Dublin City University, Dublin, Ireland
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aDepartment of Surgery, University of Rochester Medical Center, Rochester, N.Y., and
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J Vasc Res (2007) 44 (1): 75–84.
Accepted:
October 05 2006
Published Online:
December 21 2006
Abstract
Background/Aims: Resveratrol is a naturally occurring polyphenol phytoestrogen and one of several constituents of red wine thought to be cardioprotective. We investigated the effect of resveratrol on the expression of the atherogenic chemokine, monocyte chemotactic protein-1 (MCP-1). Methods: Human umbilical vein endothelial cells were stimulated with interleukin-1β (IL-1β) in the absence or presence of resveratrol. MCP-1 levels were determined by ELISA and MCP-1 mRNA was measured. Results: Resveratrol (1–100 µ_M_) dose-dependently inhibited IL-1β-stimulated MCP-1 secretion, with ∼45% inhibition at 50 µ_M_ resveratrol. This was a Gi-protein- and NO-dependent effect. Resveratrol also significantly inhibited MCP-1 gene expression in a Gi-protein-dependent but NO-independent manner. While resveratrol had no effect on MCP-1 mRNA degradation, it inhibited MCP-1 promoter activity and reduced nuclear factor ĸB and activator protein-1 binding activity induced by IL-1β. Moreover, while hemoxygenase-1 (HO-1) expression was induced by resveratrol in human umbilical vein endothelial cells, neither treatment with the HO-1 inhibitor tin-protoporphyrin IX nor siRNA-directed knockdown of HO-1 had any effect on the inhibition of MCP-1 mRNA or protein secretion by resveratrol. Conclusion: These data demonstrate an inhibitory effect of resveratrol on MCP-1 synthesis and secretion, mediated via distinct signaling pathways. The inhibition of MCP-1 may represent a novel cardioprotective mechanism of resveratrol.
References
Tunstall-Pedoe H, Kuulasmaa K, Mahonen M, Tolonen H, Ruokokoski E, Amouyel P: Contribution of trends in survival and coronary-event rates to changes in coronary heart disease mortality: 10-year results from 37 WHO MONICA project populations: monitoring trends and determinants in cardiovascular disease. Lancet 1999;353:1547–1557.
Klatsky AL, Armstrong MA, Friedman GD: Alcohol and mortality. Ann Int Med 1992;117:646–654.
Thun MJ, Peto R, Lopez AD, Monaco JH, Henley SJ, Heath, CW, Doll R: Alcohol consumption and mortality among middle-aged and elderly U.S. adults. N Engl J Med 1997;337:1705–1714.
Friedman LA, Kimball AW: Coronary heart disease mortality and alcohol consumption in Framingham. Am J Epidemiol 1986;124:481–489.
Klatsky AL, Armstrong MA: Alcoholic beverage choice and risk of coronary heart disease mortality: do red wine drinkers fare best? Am J Cardiol 1993;71:467–469.
German JB, Walzem RL: The health benefits of wine. Annu Rev Nutr 2000;20:561–593.
Mukamal KJ, Conigrave KM, Mittleman MA, Camargo CA Jr, Stampfer MJ, Willett WC, et al: Roles of drinking pattern and type of alcohol consumed in coronary heart disease in men. N Eng J Med 2003;348:109–118.
Renaud S, De Lorgeril M: Wine, alcohol, platelets, and the French paradox for coronary heart disease. Lancet 1992;339:1523–1526.
Demrow HS, Slane PR, Folts JD: Administration of wine and grape juice inhibits in vivo platelet activity and thrombosis in stenosed canine coronary arteries. Circulation 1995;91:1182–1188.
Frankel EN, Kanner J, German JB, Park E, Kinsella JE: Inhibition of oxidation of human low-density lipoprotein by phenolic substances in red wine. Lancet 1993;341:454–457.
Seimann EH, Creasey LL: Concentration of the phytoalexin resveratrol in wine. Am J Enol Vitic 1992;43:49–52.
Bavaresco L, Fregoni C, Cantu E, Trevisan M: Stilbene compounds: from the grapevine to wine. Drug Exp Clin Res 1999;25:57–63.
Wu JM, Wang ZR, Hsieh TC, Bruder JL, Zou JG, Huang YZ: Mechanism of cardioprotection by resveratrol, a phenolic antioxidant present in red wine (review). Int J Mol Med 2001;8:3–17.
Van Coillie E, Van Damme J, Opdenakker G: The MCP/eotaxin subfamily of CC chemokines. Cytokine Growth Factor Rev 1999;10:61–86.
Charo IF, Taubman MB: Chemokines in the pathogenesis of vascular disease. Circ Res 2004;95:858–866.
Aiello RJ, Bourassa PA, Lindsey S, Weng W, Natoli E, Rollins BJ, et al: Monocyte chemoattractant protein-1 accelerates atherosclerosis in apolipoprotein E-deficient mice. Arterioscler Thromb Vasc Biol 1999;19:1518–1525.
Boring L, Gosling J, Cleary M, Charo IF: Decreased lesion formation in CCR2-/- mice reveals a role for chemokines in the initiation of atherosclerosis. Nature 1998;394:894–897.
Gosling J, Slaymaker S, Gu L, Tseng S, Zlot CH, Young SG, et al: MCP-1 deficiency reduces susceptibility to atherosclerosis in mice that overexpress human apo-B. J Clin Invest 1999;103:773–778.
Ono K, Matsumori A, Furukawa Y, Igata H, Shioi T, Matsushima K, et al: Prevention of myocardial reperfusion injury in rats by an antibody against monocyte chemotactic and activating factor/monocyte chemoattractant protein-1. Lab Invest 1999;79:195–203.
Aukrust P, Ueland T, Muller F, Andreassen AK, Nordoy I, Aas H, et al: Elevated circulating levels of C-C chemokines in congestive heart failure. Circulation 1998;97:1136–1143.
Furukawa Y, Matsumori A, Ohashi N, Shioi T, Ono K, Harada A, et al: Anti-monocyte chemoattractant protein-1/monocyte chemotactic and activating factor antibody inhibits neointimal hyperplasia in injured rat carotid arteries. Circ Res 1999;306–314.
Cushing SD, Berliner JA, Valente AJ, Territo MC, Navab M, Parhami F, et al: Minimally modified low density lipoprotein induces monocyte chemotactic protein-1 in human endothelial cells and smooth muscle cells. Proc Natl Acad Sci USA 1990;87:5134–5138.
Larsen CG, Zachariae COC, Oppenheim JJ, Matsushima K: Production of monocyte chemotactic and activating factor (MCAF) by human dermal fibroblasts in response to interleukin 1 or tumor necrosis factor. Biochem Biophys Res Commun 1989;160:1403–1408.
Shyy Y, Li Y, Kolattukudy PE: Structure of human monocyte chemotactic protein gene and its regulation by TPA. Biochem Biophys Res Commun 1990;169:346–351.
Martin T, Cardarelli PM, Parry GCN, Felts KA, Cobb RR: Cytokine induction of MCP-1 gene expression in human endothelial cells depends on the cooperative action of NF-κB and AP-1. Eur J Immunol 1997;27:1091–1097.
Redmond, EM, Cullen JP, Cahill PA, Sitzmann JV, Stefansson S, Lawrence DA, et al: Endothelial cells inhibit flow-induced smooth muscle cell migration: role of plasminogen activator inhibitor-1. Circulation 2001;103:597–603.
Chang YL, Shen JJ, Wung BS, Cheng JJ, Wang DL: Chinese herbal remedy wogonin inhibits monocyte chemotactic protein-1 gene expression in human endothelial cells. Mol Pharmacol 2001;60:507–513.
Cullen JP, Sayeed S, Jin Y, Theodorakis NG, Sitzmann JV, Cahill PA, et al: Ethanol inhibits MCP-1 expression in interleukin-1β-activated human endothelial cells. Am J Physiol 2005;289:H1669–H1675.
Zou JG, Huang YZ, Chen Q, Wei EH, Hsieh TC, Wu JM: Resveratrol inhibits copper ion-induced and azo compound-initiated oxidative modification of human low density lipoprotein. Biochem Mol Biol Int 1999;47:1089–1096.
Olas B, Wachowicz B, Saluk-Juszczak J, Zielinski T: Effect of resveratrol, a natural polyphenolic compound, on platelet activation induced by endotoxin or thrombin. Thromb Res 2002;107:141–145.
Wallerath T, Deckert G, Ternes T, Anderson H, Li H, Witte K, et al: Resveratrol, a polyphenolic phytoalexin present in red wine, enhances expression and activity of endothelial nitric oxide synthase. Circulation 2002;106:1652–1658.
Di Santo A, Mezzetti A, Napoleone E, Di Tommaso R, Donati MB, De Gaetano G_,_ et al: Resveratrol and quercetin down-regulate tissue factor expression by human stimulated vascular cells. J Thromb Haemost 2003;1:1089–1095.
Carluccio MA, Siculella L, Ancora MA, Massaro M, Scoditti E, Storelli C, et al: Olive oil and red wine antioxidants polyphenols inhibit endothelial activation. Arterioscler Thromb Vasc Biol 2003;23:622–629.
Pendurthi UR, Rao LV: Resveratrol suppresses agonist-induced monocyte adhesion to cultured human endothelial cells. Thromb Res 2002;106:243–248
Ferrero ME, Bertelli AE, Fulgenzi A, Pellegatta F, Corsi MM, Bonfrate M, Ferrara F, De Caterina R, Giovannini L, Bertelli A: Activity in vitro of resveratrol on granulocyte and monocyte adhesion to endothelium. Am J Clin Nutr 1998;68:1208–1214.
Feng AN, Chen YL, Chen YT, Ding YZ, Lin SJ: Red wine inhibits MCP-1 expression and modestly reduces neointimal hyperplasia after balloon injury in cholesterol-fed rabbits. Circulation 1999;100:2254–2259.
Culpitt SV, Rogers DF, Fenwick PS, Shah P, de Matos C, Russell RE, et al: Inhibition by red wine wine extract, resveratrol, of cytokine release by alveolar macrophages in COPD. Thorax 2003;11:942–946.
Leiro J, Aranz JA, Fraiz N, Sanmartin ML, Quezada E, Orallo F: Effect of _cis_-resveratrol on genes involved in nuclear factor κ B signaling. Int Immunopharmacol 2005;5:393–406.
Kundu JK, Chun KS, Kim SO, Surh YJ: Resveratrol inhibits phorbol ester-induced cyclooxynase-2 expression in mouse skin: MAPKs and AP-1 as potential molecular targets. Biofactors 2004;21:33–39.
Klinge CM, Blankenship KA, Risinger KE, Bhatnagar S, Noisin EL, Sumanasekera WK, et al: Resveratrol and estradiol rapidly activate MAPK signaling through estrogen receptors alpha and beta in endothelial cells. J Biol Chem 2005;290:7460–7468.
Manna SK, Mukhopadhyay A, Aggarwal BB: Resveratrol suppresses TNF-induced activation of nuclear transcription factors NF-κB, activator protein-1, and apoptosis: potential role of reactive oxygen intermediates and lipid peroxidation. J Immunol 2000;15;6509–6519.
Li HF, Tian ZF, Qui XQ, Wu JX, Zhang P, Jia ZJ: A study of mechanisms involved in vasodilation induced by resveratrol in isolated porcine coronary artery. Physiol Res 2006;55:365–372.
Desai A, Miller MJ, Huang X, Warren JJ: Nitric oxide modulates MCP-1 expression in endothelial cells: implications for the pathogenesis of pulmonary granulomatous vasculitis. Inflammation 2003;27:213–223.
Goldberg DM, Yan J, Soleas GJ: Absorption of three wine-related polyphenols in three different matrices by healthy subjects. Clin Biochem 2003;36:79–87.
Morse D, Choi AMK: Heme oxygenase-1 from bench to bedside. Am J Respir Crit Care Med 2005;172:660–670.
Kaga S, Zhan L, Matsumoto M, Maulik N: Resveratrol enhances neovascularization in the infracted rat myocardium through the induction of thioredoxin-1, heme oxygenase-1 and vascular endothelial growth factor. J Mol Cell Cardiol 2005;39:813–822.
Juan SH, Cheng TH, Lin HC, Chu YL, Lee WS: Mechanism of concentration-dependent induction of heme oygenase-1 by resveratrol in human aortic smooth muscle cells. Biochem Pharmacol 2005;69:41–48.
Bowers JL, Tyulmenkov VV, Jernigan SC, Klinge CM: Resveratrol acts as a mixed agonist/antagonist for estrogen receptors α and β. Endocrinology 2000;141:3657–3667.
Rodriguez E, Lopez R, Paez A, Masso F, Montano LF: 17β-estradiol inhibits the adhesion of leukocytes in TNF-α stimulated human endothelial cells by blocking IL-8 and MCP-1 secretion, but not its transcription. Life Sci 2002;20:2181–2193.
Seli E, Pehlivan T, Selam B, Garcia-Velasco JA, Arici A: Estradiol down-regulates MCP-1 expression in human coronary artery endothelial cells. Fertil Steril 2002;77:542–547.
Kanda N, Watanabe S: 17β estradiol inhibits MCP-1 production in human keratinocytes. J Invest Dermatol 2003;120:1058–1066.
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2006
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