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Published in: European Journal of Nutrition 2/2013

01-03-2013 | Original Contribution

De-alcoholised white and red wines decrease inflammatory markers and NF-κB in atheroma plaques in apoE-deficient mice

Authors: Nuria Martínez, Kelly Casós, Paolo Simonetti, María P. Sáiz, Juan J. Moreno, María T. Mitjavila

Published in: European Journal of Nutrition | Issue 2/2013

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Abstract

Aims of the study

Wine polyphenols attenuate the development of atherosclerosis, which involves an inflammatory process. We studied the beneficial effect of de-alcoholised white and red wines (DWW and DRW, respectively) on the development of atheroma plaques and on the expression of biomarkers.

Methods

We administered control or de-alcoholised wine-rich diets to apoE-deficient mice for 12 or 20 weeks. We then used optical microscopy or immunofluorescence to examine atherosclerotic lesion development in the thoracic aorta and aortic root and assessed the presence of cytokines and adhesion molecules by qPCR and immunofluorescence in total aorta and aortic root, respectively.

Results

Atherosclerotic lesions in thoracic aorta were significantly decreased in mice supplemented with DWW (30 %) and DRW (62 %) for 20 weeks. In addition, the expressions of interferon-γ, interleukin-1β, the monocyte chemoattractant protein-1 and CD68 were reduced by DRW. The adhesion molecule P-selectin, vascular cell adhesion molecule-1 and intercellular adhesion molecule-1 were decreased by 52, 76 and 45 %, respectively, in mice fed DRW for 12 weeks, whereas DWW reduced these parameters in a minor extent. The NF-κB expression in total aorta was significantly decreased in the mice treated with de-alcoholised wines for 12 weeks.

Conclusions

DRW is shown to be more effective than DWW on cytokines and adhesion molecule expression, in the early stages of the inflammatory events associated with atherosclerosis development, probably due to the high phenolic content of red wine. Downregulation of NF-κB expression may be involved in the mechanism by which de-alcoholised wines modulate atherosclerosis.
Literature
1.
go back to reference Libby P, Sukhova G, Lee RT, Galis ZS (1995) Cytokines regulate vascular functions related to stability of the atherosclerotic plaque. J Cardiovasc Pharmacol 25(Suppl 2):S9–S12CrossRef Libby P, Sukhova G, Lee RT, Galis ZS (1995) Cytokines regulate vascular functions related to stability of the atherosclerotic plaque. J Cardiovasc Pharmacol 25(Suppl 2):S9–S12CrossRef
2.
go back to reference Girn HR, Orsi NM, Homer-Vanniasinkam S (2007) An overview of cytokine interactions in atherosclerosis and implications for peripheral arterial disease. Vasc Med 12(4):299–309CrossRef Girn HR, Orsi NM, Homer-Vanniasinkam S (2007) An overview of cytokine interactions in atherosclerosis and implications for peripheral arterial disease. Vasc Med 12(4):299–309CrossRef
3.
go back to reference McEver RP (2002) Selectins: lectins that initiate cell adhesion under flow. Curr Opin Cell Biol 14(5):581–586CrossRef McEver RP (2002) Selectins: lectins that initiate cell adhesion under flow. Curr Opin Cell Biol 14(5):581–586CrossRef
4.
go back to reference Adams DH, Shaw S (1994) Leucocyte-endothelial interactions and regulation of leucocyte migration. Lancet 343(8901):831–836CrossRef Adams DH, Shaw S (1994) Leucocyte-endothelial interactions and regulation of leucocyte migration. Lancet 343(8901):831–836CrossRef
5.
go back to reference Barnes PJ, Karin M (1997) Nuclear factor-kappaB: a pivotal transcription factor in chronic inflammatory diseases. N Engl J Med 336(15):1066–1071CrossRef Barnes PJ, Karin M (1997) Nuclear factor-kappaB: a pivotal transcription factor in chronic inflammatory diseases. N Engl J Med 336(15):1066–1071CrossRef
6.
go back to reference Rice-Evans CA, Miller NJ, Paganga G (1996) Structure-antioxidant activity relationships of flavonoids and phenolic acids. Free Rad Biol Med 20(7):933–956CrossRef Rice-Evans CA, Miller NJ, Paganga G (1996) Structure-antioxidant activity relationships of flavonoids and phenolic acids. Free Rad Biol Med 20(7):933–956CrossRef
7.
go back to reference Dal-Ros S, Zoll J, Lang AL, Auger C, Keller N, Bronner C, Geny B, Schini-Kerth VB (2011) Chronic intake of red wine polyphenols by young rats prevents aging-induced endothelial dysfunction and decline in physical performance: role of NADPH oxidase. Biochem Biophys Res Commun 404(2):743–749CrossRef Dal-Ros S, Zoll J, Lang AL, Auger C, Keller N, Bronner C, Geny B, Schini-Kerth VB (2011) Chronic intake of red wine polyphenols by young rats prevents aging-induced endothelial dysfunction and decline in physical performance: role of NADPH oxidase. Biochem Biophys Res Commun 404(2):743–749CrossRef
8.
go back to reference Stocker R, O’Halloran RA (2004) Dealcoholized red wine decreases atherosclerosis in apolipoprotein E gene-deficient mice independently of inhibition of lipid peroxidation in the artery wall. Am J Clin Nutr 79(1):123–130 Stocker R, O’Halloran RA (2004) Dealcoholized red wine decreases atherosclerosis in apolipoprotein E gene-deficient mice independently of inhibition of lipid peroxidation in the artery wall. Am J Clin Nutr 79(1):123–130
9.
go back to reference Renaud S, de Lorgeril M (1992) Wine, alcohol, platelets, and the French paradox for coronary heart disease. Lancet 339(8808):1523–1526CrossRef Renaud S, de Lorgeril M (1992) Wine, alcohol, platelets, and the French paradox for coronary heart disease. Lancet 339(8808):1523–1526CrossRef
10.
go back to reference Hertog MG, Kromhout D, Aravanis C, Blackburn H, Buzina R, Fidanza F, Giampaoli S, Jansen A, Menotti A, Nedeljkovic S et al (1995) Flavonoid intake and long-term risk of coronary heart disease and cancer in the seven countries study. Arch Intern Med 155(4):381–386CrossRef Hertog MG, Kromhout D, Aravanis C, Blackburn H, Buzina R, Fidanza F, Giampaoli S, Jansen A, Menotti A, Nedeljkovic S et al (1995) Flavonoid intake and long-term risk of coronary heart disease and cancer in the seven countries study. Arch Intern Med 155(4):381–386CrossRef
11.
go back to reference Carluccio MA, Siculella L, Ancora MA, Massaro M, Scoditti E, Storelli C, Visioli F, Distante A, De Caterina R (2003) Olive oil and red wine antioxidant polyphenols inhibit endothelial activation: antiatherogenic properties of Mediterranean diet phytochemicals. Arterioscl Thromb Vasc Biol 23(4):622–629CrossRef Carluccio MA, Siculella L, Ancora MA, Massaro M, Scoditti E, Storelli C, Visioli F, Distante A, De Caterina R (2003) Olive oil and red wine antioxidant polyphenols inhibit endothelial activation: antiatherogenic properties of Mediterranean diet phytochemicals. Arterioscl Thromb Vasc Biol 23(4):622–629CrossRef
12.
go back to reference Ludwig A, Lorenz M, Grimbo N, Steinle F, Meiners S, Bartsch C, Stangl K, Baumann G, Stangl V (2004) The tea flavonoid epigallocatechin-3-gallate reduces cytokine-induced VCAM-1 expression and monocyte adhesion to endothelial cells. Biochem Biophys Res Commun 316(3):659–665CrossRef Ludwig A, Lorenz M, Grimbo N, Steinle F, Meiners S, Bartsch C, Stangl K, Baumann G, Stangl V (2004) The tea flavonoid epigallocatechin-3-gallate reduces cytokine-induced VCAM-1 expression and monocyte adhesion to endothelial cells. Biochem Biophys Res Commun 316(3):659–665CrossRef
13.
go back to reference Lopez D, Pavelkova M, Gallova L, Simonetti P, Gardana C, Lojek A, Loaiza R, Mitjavila MT (2007) Dealcoholized red and white wines decrease oxidative stress associated with inflammation in rats. Br J Nutr 98(3):611–619CrossRef Lopez D, Pavelkova M, Gallova L, Simonetti P, Gardana C, Lojek A, Loaiza R, Mitjavila MT (2007) Dealcoholized red and white wines decrease oxidative stress associated with inflammation in rats. Br J Nutr 98(3):611–619CrossRef
14.
go back to reference Norata GD, Marchesi P, Passamonti S, Pirillo A, Violi F, Catapano AL (2007) Anti-inflammatory and anti-atherogenic effects of cathechin, caffeic acid and trans-resveratrol in apolipoprotein E deficient mice. Atherosclerosis 191(2):265–271CrossRef Norata GD, Marchesi P, Passamonti S, Pirillo A, Violi F, Catapano AL (2007) Anti-inflammatory and anti-atherogenic effects of cathechin, caffeic acid and trans-resveratrol in apolipoprotein E deficient mice. Atherosclerosis 191(2):265–271CrossRef
15.
go back to reference Emeson EE, Manaves V, Singer T, Tabesh M (1995) Chronic alcohol feeding inhibits atherogenesis in C57BL/6 hyperlipidemic mice. Am J Pathol 147(6):1749–1758 Emeson EE, Manaves V, Singer T, Tabesh M (1995) Chronic alcohol feeding inhibits atherogenesis in C57BL/6 hyperlipidemic mice. Am J Pathol 147(6):1749–1758
16.
go back to reference Jawien J, Nastalek P, Korbut R (2004) Mouse models of experimental atherosclerosis. J Physiol Pharmacol 55(3):503–517 Jawien J, Nastalek P, Korbut R (2004) Mouse models of experimental atherosclerosis. J Physiol Pharmacol 55(3):503–517
17.
go back to reference Benito S, Lopez D, Saiz MP, Buxaderas S, Sanchez J, Puig-Parellada P, Mitjavila MT (2002) A flavonoid-rich diet increases nitric oxide production in rat aorta. Br J Pharmacol 135(4):910–916CrossRef Benito S, Lopez D, Saiz MP, Buxaderas S, Sanchez J, Puig-Parellada P, Mitjavila MT (2002) A flavonoid-rich diet increases nitric oxide production in rat aorta. Br J Pharmacol 135(4):910–916CrossRef
18.
go back to reference Singleton VL, Rossi JA (1965) Colorimetry of total phenolics with phosphomolybdic-phosphotungstic acid reagents. Am J Enol Viticult 16:144–158 Singleton VL, Rossi JA (1965) Colorimetry of total phenolics with phosphomolybdic-phosphotungstic acid reagents. Am J Enol Viticult 16:144–158
19.
go back to reference Osawa T (1999) Protective role of dietary polyphenols in oxidative stress. Mech Ageing Dev 111(2–3):133–139CrossRef Osawa T (1999) Protective role of dietary polyphenols in oxidative stress. Mech Ageing Dev 111(2–3):133–139CrossRef
20.
go back to reference Pinkel D (1958) The use of body surface area as a criterion of drug dosage in cancer chemotherapy. Cancer Res 18(7):853–856 Pinkel D (1958) The use of body surface area as a criterion of drug dosage in cancer chemotherapy. Cancer Res 18(7):853–856
21.
go back to reference Casos K, Saiz MP, Ruiz-Sanz JI, Mitjavila MT (2008) Atherosclerosis prevention by a fish oil-rich diet in apoE(−/−) mice is associated with a reduction of endothelial adhesion molecules. Atherosclerosis 201(2):306–317CrossRef Casos K, Saiz MP, Ruiz-Sanz JI, Mitjavila MT (2008) Atherosclerosis prevention by a fish oil-rich diet in apoE(−/−) mice is associated with a reduction of endothelial adhesion molecules. Atherosclerosis 201(2):306–317CrossRef
22.
go back to reference Mahley RW, Rall SC Jr (2000) Apolipoprotein E: far more than a lipid transport protein. Ann Rev Genom Hum Genetics 1:507–537CrossRef Mahley RW, Rall SC Jr (2000) Apolipoprotein E: far more than a lipid transport protein. Ann Rev Genom Hum Genetics 1:507–537CrossRef
23.
go back to reference Waddington E, Puddey IB, Croft KD (2004) Red wine polyphenolic compounds inhibit atherosclerosis in apolipoprotein E-deficient mice independently of effects on lipid peroxidation. Am J Clin Nutr 79(1):54–61 Waddington E, Puddey IB, Croft KD (2004) Red wine polyphenolic compounds inhibit atherosclerosis in apolipoprotein E-deficient mice independently of effects on lipid peroxidation. Am J Clin Nutr 79(1):54–61
24.
go back to reference Frangos SG, Gahtan V, Sumpio B (1999) Localization of atherosclerosis: role of hemodynamics. Arch Surg 134(10):1142–1149CrossRef Frangos SG, Gahtan V, Sumpio B (1999) Localization of atherosclerosis: role of hemodynamics. Arch Surg 134(10):1142–1149CrossRef
25.
go back to reference Mitsuhashi H, Ikeuchi H, Nojima Y (2001) Is sulfite an antiatherogenic compound in wine? Clin Chem 47(10):1872–1873 Mitsuhashi H, Ikeuchi H, Nojima Y (2001) Is sulfite an antiatherogenic compound in wine? Clin Chem 47(10):1872–1873
26.
go back to reference Lotito SB, Frei B (2004) The increase in human plasma antioxidant capacity after apple consumption is due to the metabolic effect of fructose on urate, not apple-derived antioxidant flavonoids. Free Rad Biol Med 37(2):251–258CrossRef Lotito SB, Frei B (2004) The increase in human plasma antioxidant capacity after apple consumption is due to the metabolic effect of fructose on urate, not apple-derived antioxidant flavonoids. Free Rad Biol Med 37(2):251–258CrossRef
27.
go back to reference Loke WM, Proudfoot JM, Hodgson JM, McKinley AJ, Hime N, Magat M, Stocker R, Croft KD (2010) Specific dietary polyphenols attenuate atherosclerosis in apolipoprotein E-knockout mice by alleviating inflammation and endothelial dysfunction. Arterioscl Thromb Vasc Biol 30(4):749–757CrossRef Loke WM, Proudfoot JM, Hodgson JM, McKinley AJ, Hime N, Magat M, Stocker R, Croft KD (2010) Specific dietary polyphenols attenuate atherosclerosis in apolipoprotein E-knockout mice by alleviating inflammation and endothelial dysfunction. Arterioscl Thromb Vasc Biol 30(4):749–757CrossRef
28.
go back to reference Cullen JP, Morrow D, Jin Y, Curley B, Robinson A, Sitzmann JV, Cahill PA, Redmond EM (2007) Resveratrol, a polyphenolic phytostilbene, inhibits endothelial monocyte chemotactic protein-1 synthesis and secretion. J Vasc Res 44(1):75–84CrossRef Cullen JP, Morrow D, Jin Y, Curley B, Robinson A, Sitzmann JV, Cahill PA, Redmond EM (2007) Resveratrol, a polyphenolic phytostilbene, inhibits endothelial monocyte chemotactic protein-1 synthesis and secretion. J Vasc Res 44(1):75–84CrossRef
29.
go back to reference Garcia-Alonso M, Minihane AM, Rimbach G, Rivas-Gonzalo JC, de Pascual-Teresa S (2009) Red wine anthocyanins are rapidly absorbed in humans and affect monocyte chemoattractant protein 1 levels and antioxidant capacity of plasma. J Nutr Biochem 20(7):521–529CrossRef Garcia-Alonso M, Minihane AM, Rimbach G, Rivas-Gonzalo JC, de Pascual-Teresa S (2009) Red wine anthocyanins are rapidly absorbed in humans and affect monocyte chemoattractant protein 1 levels and antioxidant capacity of plasma. J Nutr Biochem 20(7):521–529CrossRef
30.
go back to reference Vivancos M, Moreno JJ (2008) Effect of resveratrol, tyrosol and beta-sitosterol on oxidised low-density lipoprotein-stimulated oxidative stress, arachidonic acid release and prostaglandin E2 synthesis by RAW 264.7 macrophages. Br J Nutr 99(6):1199–1207CrossRef Vivancos M, Moreno JJ (2008) Effect of resveratrol, tyrosol and beta-sitosterol on oxidised low-density lipoprotein-stimulated oxidative stress, arachidonic acid release and prostaglandin E2 synthesis by RAW 264.7 macrophages. Br J Nutr 99(6):1199–1207CrossRef
31.
32.
go back to reference Sacanella E, Vazquez-Agell M, Mena MP, Antunez E, Fernandez-Sola J, Nicolas JM, Lamuela-Raventos RM, Ros E, Estruch R (2007) Down-regulation of adhesion molecules and other inflammatory biomarkers after moderate wine consumption in healthy women: a randomized trial. Am J Clin Nutr 86(5):1463–1469 Sacanella E, Vazquez-Agell M, Mena MP, Antunez E, Fernandez-Sola J, Nicolas JM, Lamuela-Raventos RM, Ros E, Estruch R (2007) Down-regulation of adhesion molecules and other inflammatory biomarkers after moderate wine consumption in healthy women: a randomized trial. Am J Clin Nutr 86(5):1463–1469
33.
go back to reference Cybulsky MI, Iiyama K, Li H, Zhu S, Chen M, Iiyama M, Davis V, Gutierrez-Ramos JC, Connelly PW, Milstone DS (2001) A major role for VCAM-1, but not ICAM-1, in early atherosclerosis. J Clin Invest 107(10):1255–1262CrossRef Cybulsky MI, Iiyama K, Li H, Zhu S, Chen M, Iiyama M, Davis V, Gutierrez-Ramos JC, Connelly PW, Milstone DS (2001) A major role for VCAM-1, but not ICAM-1, in early atherosclerosis. J Clin Invest 107(10):1255–1262CrossRef
34.
go back to reference Iiyama K, Hajra L, Iiyama M, Li H, DiChiara M, Medoff BD, Cybulsky MI (1999) Patterns of vascular cell adhesion molecule-1 and intercellular adhesion molecule-1 expression in rabbit and mouse atherosclerotic lesions and at sites predisposed to lesion formation. Circulation Res 85(2):199–207CrossRef Iiyama K, Hajra L, Iiyama M, Li H, DiChiara M, Medoff BD, Cybulsky MI (1999) Patterns of vascular cell adhesion molecule-1 and intercellular adhesion molecule-1 expression in rabbit and mouse atherosclerotic lesions and at sites predisposed to lesion formation. Circulation Res 85(2):199–207CrossRef
35.
go back to reference Wung BS, Hsu MC, Wu CC, Hsieh CW (2005) Resveratrol suppresses IL-6-induced ICAM-1 gene expression in endothelial cells: effects on the inhibition of STAT3 phosphorylation. Life Sci 78(4):389–397CrossRef Wung BS, Hsu MC, Wu CC, Hsieh CW (2005) Resveratrol suppresses IL-6-induced ICAM-1 gene expression in endothelial cells: effects on the inhibition of STAT3 phosphorylation. Life Sci 78(4):389–397CrossRef
36.
go back to reference Bharti AC, Aggarwal BB (2002) Nuclear factor-kappa B and cancer: its role in prevention and therapy. Biochem Pharmacol 64(5–6):883–888CrossRef Bharti AC, Aggarwal BB (2002) Nuclear factor-kappa B and cancer: its role in prevention and therapy. Biochem Pharmacol 64(5–6):883–888CrossRef
37.
go back to reference Canali R, Comitato R, Ambra R, Virgili F (2010) Red wine metabolites modulate NF-kappaB, activator protein-1 and cAMP response element-binding proteins in human endothelial cells. Br J Nutr 103(6):807–814CrossRef Canali R, Comitato R, Ambra R, Virgili F (2010) Red wine metabolites modulate NF-kappaB, activator protein-1 and cAMP response element-binding proteins in human endothelial cells. Br J Nutr 103(6):807–814CrossRef
38.
go back to reference Blanco-Colio LM, Valderrama M, Alvarez-Sala LA, Bustos C, Ortego M, Hernandez-Presa MA, Cancelas P, Gomez-Gerique J, Millan J, Egido J (2000) Red wine intake prevents nuclear factor-kappaB activation in peripheral blood mononuclear cells of healthy volunteers during postprandial lipemia. Circulation 102(9):1020–1026CrossRef Blanco-Colio LM, Valderrama M, Alvarez-Sala LA, Bustos C, Ortego M, Hernandez-Presa MA, Cancelas P, Gomez-Gerique J, Millan J, Egido J (2000) Red wine intake prevents nuclear factor-kappaB activation in peripheral blood mononuclear cells of healthy volunteers during postprandial lipemia. Circulation 102(9):1020–1026CrossRef
39.
go back to reference Choi KH, Kim JE, Song NR, Son JE, Hwang MK, Byun S, Kim JH, Lee KW, Lee HJ (2010) Phosphoinositide 3-kinase is a novel target of piceatannol for inhibiting PDGF-BB-induced proliferation and migration in human aortic smooth muscle cells. Cardiovasc Res 85(4):836–844CrossRef Choi KH, Kim JE, Song NR, Son JE, Hwang MK, Byun S, Kim JH, Lee KW, Lee HJ (2010) Phosphoinositide 3-kinase is a novel target of piceatannol for inhibiting PDGF-BB-induced proliferation and migration in human aortic smooth muscle cells. Cardiovasc Res 85(4):836–844CrossRef
40.
go back to reference Iijima K, Yoshizumi M, Hashimoto M, Akishita M, Kozaki K, Ako J, Watanabe T, Ohike Y, Son B, Yu J, Nakahara K, Ouchi Y (2002) Red wine polyphenols inhibit vascular smooth muscle cell migration through two distinct signaling pathways. Circulation 105(20):2404–2410CrossRef Iijima K, Yoshizumi M, Hashimoto M, Akishita M, Kozaki K, Ako J, Watanabe T, Ohike Y, Son B, Yu J, Nakahara K, Ouchi Y (2002) Red wine polyphenols inhibit vascular smooth muscle cell migration through two distinct signaling pathways. Circulation 105(20):2404–2410CrossRef
Metadata
Title
De-alcoholised white and red wines decrease inflammatory markers and NF-κB in atheroma plaques in apoE-deficient mice
Authors
Nuria Martínez
Kelly Casós
Paolo Simonetti
María P. Sáiz
Juan J. Moreno
María T. Mitjavila
Publication date
01-03-2013
Publisher
Springer-Verlag
Published in
European Journal of Nutrition / Issue 2/2013
Print ISSN: 1436-6207
Electronic ISSN: 1436-6215
DOI
https://doi.org/10.1007/s00394-012-0379-4

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