Hostname: page-component-cd9895bd7-q99xh Total loading time: 0 Render date: 2024-12-27T12:32:01.449Z Has data issue: false hasContentIssue false
  • English
  • Français

Monocyte chemoattractant protein-1 involvement in the α-tocopherol-induced reduction of atherosclerotic lesions in apolipoprotein E knockout mice

Published online by Cambridge University Press:  07 June 2007

Maria C. G. Peluzio ,
Emir Miguel Jr ,
Thaís C. Drumond ,
Giovana C. César ,
Helton C. Santiago ,
Mauro M. Teixeira ,
Enio C. Vieira ,
Rosa M. E. Arantes  and
Jacqueline I. Alvarez-Leite
Maria C. G. Peluzio
Affiliation:
Departamento de Nutrição e Saúde, Universidade Federal de Viçosa, Av PH Rolls s/n. 36570-000, Brazil
Emir Miguel Jr
Affiliation:
Departamento de Bioquímica e Imunologia, ICB, Universidade Federal de Minas Gerais, Caixa Postal 486, 30 161-970, Belo Horizonte–MG, Brazil
Thaís C. Drumond
Affiliation:
Departamento de Bioquímica e Imunologia, ICB, Universidade Federal de Minas Gerais, Caixa Postal 486, 30 161-970, Belo Horizonte–MG, Brazil
Giovana C. César
Affiliation:
Departamento de Bioquímica e Imunologia, ICB, Universidade Federal de Minas Gerais, Caixa Postal 486, 30 161-970, Belo Horizonte–MG, Brazil
Helton C. Santiago
Affiliation:
Departamento de Bioquímica e Imunologia, ICB, Universidade Federal de Minas Gerais, Caixa Postal 486, 30 161-970, Belo Horizonte–MG, Brazil
Mauro M. Teixeira
Affiliation:
Departamento de Bioquímica e Imunologia, ICB, Universidade Federal de Minas Gerais, Caixa Postal 486, 30 161-970, Belo Horizonte–MG, Brazil
Enio C. Vieira
Affiliation:
Departamento de Bioquímica e Imunologia, ICB, Universidade Federal de Minas Gerais, Caixa Postal 486, 30 161-970, Belo Horizonte–MG, Brazil
Rosa M. E. Arantes
Affiliation:
Departamento de Patologia Geral, ICB, Universidade Federal de Minas Gerais, Caixa Postal 486, 30 161-970, Belo Horizonte–MG, Brazil
Jacqueline I. Alvarez-Leite*
Affiliation:
Departamento de Bioquímica e Imunologia, ICB, Universidade Federal de Minas Gerais, Caixa Postal 486, 30 161-970, Belo Horizonte–MG, Brazil
*
*Corresponding author: Dr Jacqueline I. Alvarez-Leite, fax +55 31 441 5963, email alvarez@ufmg.br
Rights & Permissions [Opens in a new window]

Abstract

Core share and HTML view are not available for this content. However, as you have access to this content, a full PDF is available via the ‘Save PDF’ action button.

We studied the effects of α-tocopheryl acetate supplementation on the development of fatty streaks and its ability to modulate the expression of monocyte chemoattractant protein (MCP)-1 in aortic lesions of apoliprotein E knockout mice. For this purpose, 16-week-old apolipoprotein E knockout mice received α-tocopherol supplemention ((800 mg)/kg diet) for 6 weeks. After this time, total and lipoprotein cholesterol in the serum, hepatic tocopherol, aortic lesion area and MCP-1 (protein and mRNA) expression were analysed. Our present results showed that the dietary supplementation with α-tocopherol did not reduce serum cholesterol nor change lipoprotein profile, but it reduced the area of the aortic lesion by 55%. The reduction in the lesion size was correlated with the reduced expression of MCP-1 mRNA and protein, as detected by real-time quantitative polymerase chain reaction and immunohistochemistry respectively. In conclusion, the results obtained here are relevant to the study of atherosclerosis, as they correlate the effectiveness of vitamin E supplementation in inhibiting the plaque formation with diminished expression of MCP-1 at the aortic lesion.

Keywords

AtherosclerosisApolipoprotein E knockout miceα-TocopherolMonocyte chemoattractant protein-1Antioxidant
Type
Research Article
Information
British Journal of Nutrition , Volume 90 , Issue 1 , July 2003 , pp. 3 - 11
Copyright
Copyright © The Nutrition Society 2003

References

Aiello, RJ, Bourassa, P-AK, Lindsey, S, et al. (1999) Monocyte chemoattractant protein-1 accelerates atherosclerosis in apolipoprotein E-deficient mice. Arterioscler Thromb Vasc Biol 19, 1518–1525.CrossRefGoogle ScholarPubMed
Allain, CC, Poon, LS, Chan, CSG, Richmond, W & Fu, PC (1974) Enzymatic determination of total serum cholesterol. Clin Chem 20, 470–475.CrossRefGoogle ScholarPubMed
Asmis, R & Jelk, J (2000) Vitamin E suplementation of human macrophages prevents neither foam cell formation nor increased susceptibility of foam cells to lysis by oxidized LDL. Arterioscler Thromb Vasc Biol 20, 2078–2086.CrossRefGoogle Scholar
Azen, SP, Qian, D, Mack, WJ, et al. (1996) Effect of supplementary antioxidant vitamin intake on carotid arterial wall intima-media thickness in a controlled clinical trial of cholesterol lowering. Circulation 94, 2369–2372.CrossRefGoogle Scholar
Boaz, M, Smetana, S, Weinstein, T, et al. (2000) Secondary prevention with antioxidants of cardiovascular disease in endstage renal disease (SPACE): randomised placebo-controlled trial. Lancet 356, 1213–1218.CrossRefGoogle ScholarPubMed
Boisvert, WA, Black, AS & Curtiss, LK (1999) Apo A1 reduces free cholesterol accumulation in atherosclerosis lesions of apo E-deficient mice transplanted with apo E-expressing macrophages. Arterioscler Thromb Vasc Biol 19, 525–530.CrossRefGoogle Scholar
Boring, L, Gosling, J, Cleary, M & Charo, IF (1998) Decreases lesion formation in CCR2- mice reveals a role for chemokines in the formatin of atherosclerosis. Nature 394, 894–897.CrossRefGoogle Scholar
Brown, BG, Cheung, MC, Lee, AC, Zhao, XQ & Chait, A (2002) Antioxidant vitamins and lipid therapy: end of a long romance?. Arterioscler Thromb Vasc Biol 22, 1535–1546.CrossRefGoogle ScholarPubMed
Brown, BG, Zhao, XQ, Chait, A, et al. (2001) Simvastatin and niacin, antioxidant vitamins, or the combination for the prevention of coronary disease. New Eng J Med 345, 1583–1592.CrossRefGoogle ScholarPubMed
Chisolm, GM & Steinberg, D (2000) The oxidative modification hypothesis of atherogenesis: an overview. Free Radic Biol Med 28, 1815–1826.CrossRefGoogle ScholarPubMed
Collaborative Group of the Primary Prevention Project (2001) Low-dose aspirin and vitamin E in people at cardiovascular risk: a randomized trial in general practice. Lancet 357, 89–95.CrossRefGoogle Scholar
Crawford, RS, Kirk, EA, Rosenfeld, ME, LeBoeuf, RC & Chait, A (1998) Dietary antioxidants inhibit development of fatty streak lesions in the LDL receptor-deficient mouse. Arterioscler Thromb Vasc Biol 18, 1506–1513.CrossRefGoogle ScholarPubMed
Devaraj, S, Harris, A & Jialal, I (2002) Modulation of monocyte-macrophage function with α-tocopherol: implications for atherosclerosis. Nutr Rev 60, 8–13.CrossRefGoogle ScholarPubMed
Djahansouzi, S, Braesen, JH, Koenig, K, Beisiegel, V & Kontush, A (2001) The effect of phamacological doses of different antioxidants on oxidation parameters and atherogenesis in hyperlipidaemic rabbits. Atherosclerosis 154, 387–398.CrossRefGoogle Scholar
Fazio, S, Babaev, VR, Murray, AB, et al. (1997) Increased atherosclerosis in mice reconstituted with apolipoprotein E null macrophages. Proc Natl Acad Sci USA 94, 4647–4652.CrossRefGoogle ScholarPubMed
Folch, J, Lees, M & Stanley, S (1957) A simple method for the isolation and purification of total lipides from animal tissues. J Biol Chem 226, 497–509.CrossRefGoogle ScholarPubMed
Frei, B (1999) On the role of vitamin C and other antioxidants in atherogenesis and vascular dysfunction. Proc Soc Exp Biol Med 222, 196–204.CrossRefGoogle ScholarPubMed
GISSI-Prevenzione Investigators (1999) Dietary supplementation with n-3 polyunsaturated fatty acids and vitamin E after myocardial infarction: results of the GISSI-Prevenzione trial. Lancet 354, 447–455.CrossRefGoogle Scholar
Giulietti, A, Overbergh, L, Valckx, D, Decallonne, B, Bouillon, R & Mathieu, C (2001) An overview of real-time quantitative PCR: Applications to quantify cytokine gene expression. Methods 25, 386–401.CrossRefGoogle ScholarPubMed
Gu, L, Okada, Y, Clinton, SK, et al. (1998) Absence of monocyte chemoattractant protein 1 reduces atherosclerosis in low density lipoprotein receptor-deficient mice. Mol Cell 2, 275–281.CrossRefGoogle ScholarPubMed
Hayek, T, Oiknine, J, Brook, JG & Aviram, M (1994) Increased plasma and lipoprotein lipid peroxidation in Apo-E deficient mice. Biochem Biophys Res Comm 3, 1567–1574.CrossRefGoogle Scholar
Heinecke, JW (2001) Is the emperor wearing clothes? Clinical trials of vitamin E and the LDL oxidation hypothesis. Arterioscler Thromb Vasc Biol 21, 1261–1264.CrossRefGoogle ScholarPubMed
Hodis, HN, Mack, WJ & LaBree, L (2002) Alpha-tocopherol supplementation in healthy individuals reduces low-density lipoprotein oxidation but not atherosclerosis: the Vitamin Atherosclerosis Prevention Study (VEAPS). Circulation 106, 1453–1459.CrossRefGoogle Scholar
Hodis, HN, Mack, WJ, LaBree, L, et al. (1995) Serial coronary angiographic evidence that antioxidant vitamin intake reduces progression of coronary artery atherosclerosis. JAMA 273, 1849–1854.CrossRefGoogle ScholarPubMed
Howard, HN, Wendy, MJ, LaBree, L, et al. (2002) Alpha-tocopherol supplementation in healthy individuals reduces low-density lipoprotein oxidation but not atherosclerosis: The Vitamin E Atherosclerosis Prevention Study (VEAPS). Circulation 106, 1453–1459.Google Scholar
Huang, HY, Appel, LJ, Croft, KD, Miller, ER 3rd, Mori, TA & Puddey, IB (2002) Effects of vitamin C and vitamin E on in vivo lipid peroxidation: results of a randomized controlled trial. Am J Clin Nutr 76, 549–555.CrossRefGoogle ScholarPubMed
Iuliano, L, Micheletta, F, Maranghi, M, Frati, G, Diczfalusy, U & Violi, F (2001) Bioavailability of vitamin E as function of food intake in healthy subjects: effects on plasma peroxide-scavenging activity and cholesterol-oxidation products. Arterioscler Thromb Vasc Biol 21, e34–e37.CrossRefGoogle ScholarPubMed
Kayden, HJ & Traber, MG (1993) Absorption, lipoprotein transport and regulation of plasma concentrations of vitamin E in humans. J Lipid Res 34, 343–358.CrossRefGoogle ScholarPubMed
Landmesser, U & Harrison, DG (2001) Oxidant stress as a marker for cardiovascular events: Ox marks or spot. Circulation 104, 2638–2640.CrossRefGoogle ScholarPubMed
Libby, P, Geng, YJ, Masanori, A, et al. (1996) Macrophages and atherosclerotic plaque stability. Curr Opin Lipidol 7, 330–335.CrossRefGoogle ScholarPubMed
Lonn, E, Yusuf, S, Dzavik, V, et al. (2001) Effects of ramipril and vitamin E on atherosclerosis: the study to evaluate carotid ultrasound changes in patients treated with ramipril and vitamin E (SECURE). Circulation 103, 919–925.CrossRefGoogle Scholar
McCall, MR & Frei, B (1999) Can antioxidant vitamins materially reduce oxidative damage in humans?. Free Radic Biol Med 26, 1034–1053.CrossRefGoogle ScholarPubMed
Munday, JS, Thompson, KG, James, KAC & Manktelow, BW (1998) Dietary antioxidants do not reduce fatty streak formation in the C57BL/6 mouse atherosclerosis model. Arterioscler Thromb Vasc Biol 18, 114–119.CrossRefGoogle Scholar
Nakashima, Y, Plump, AS, Raines, EW, Breslow, JL & Ross, R (1994) Apo E-deficient mice develop lesions of all phases of atherosclerosis throughout the arterial tree. Arterioscler Thromb Vasc Biol 14, 133–140.CrossRefGoogle ScholarPubMed
Nelken, NA, Coughlin, SR, Gordon, D & Wilcox, JN (1991) Monocyte chemoattractant protein-1 in human atheromatous plaques. J Clin Invest 88, 1121–1127.CrossRefGoogle ScholarPubMed
Overbergh, L, Valckx, D, Waer, M & Mathieu, C (1998) Quantification of murine citokine mRNAs using real-time quantitative reverse transcriptase PCR. Cytokine 11, 305–312.CrossRefGoogle Scholar
Packer, L (1991) Protective role of vitamin E in biological systems. Am J Clin Nutr 53, 1050S-1055S.CrossRefGoogle ScholarPubMed
Paigen, B, Morrow, A, Holmes, PA, Mitchell, D & Williams, A (1987) Quantitative assessment of atherosclerosis lesions in mice. Atherosclerosis 68, 231–240.CrossRefGoogle ScholarPubMed
Parthasarathy, S, Santanam, N & Augé, N (1998) Oxidized low-density lipoprotein, a two-faced Janus in coronary artery disease?. Biochem Pharmacol 56, 279–284.CrossRefGoogle ScholarPubMed
Peluzio, MCG, Homen, APP & Cesar, GC (2001) Influences of α-tocopherol on cholesterol metabolism and fatty streak development in apo E deficient atherogenic diet. Braz J Med Biol Res 35, 161–173.Google Scholar
Phonpanichrasamee, C, Komaratat, P & Wilairat, P (1990) Hypocholesterolemic effect of vitamin E on cholesterol-fed rabbit. Int J Vitam Nutr Res 60, 240–244.Google ScholarPubMed
Praticò, D, Tangirala, RK, Rader, DJ, Rokach, J & FitzGerald, GA (1998) Vitamin E supresses isoprostane generation in vivo and reduces atherosclerosis in Apo-E deficient mice. Nat Med 10, 1189–1192.CrossRefGoogle Scholar
Reddick, RL, Zhang, SH & Maeda, N (1994) Atherosclerosis in mice lacking apo E. Evaluation of lesional development and progression. Arterioscler Thromb Vasc Biol 14, 141–147.CrossRefGoogle ScholarPubMed
Reeves, PG, Nielsen, FH & Fahey, GC Jr (1993) AIN-93 purified diets for laboratory rodents: final report of the American Institute of Nutrition ad hoc writing committee on the reformulation of the AIN-76A rodent diet. J Nutr 123, 1936–1951.CrossRefGoogle Scholar
Ricciarelli, R, Zing, JM & Azzi, A (2002) The 80th anniversary of vitamin E: beyond its antioxidant properties. Biol Chem 383, 57–65.CrossRefGoogle ScholarPubMed
Rilley, JS & Stouffer, GA (2002) The antioxidant vitamins and coronary heart disease: Part I. Basic science background and clinical observational studies. Am J Med Sci 324, 314–320.Google Scholar
Rimm, EB, Stampfer, MJ, Ascherio, A, Giovannucci, E, Colditz, GA & Willett, WC (1993) Vitamin E consumption and the risk of coronary heart disease in men. New Eng J Med 328, 1450–1456.CrossRefGoogle ScholarPubMed
Salonen, JT, Nyyssonen, K, Salonen, R, et al. (2000) Antioxidant supplementation in atherosclerosis prevention (ASAP) study: a randomized trial of the effect of vitamins E and C on 3-year progression of carotid atherosclerosis. J Int Med 248, 377–386.CrossRefGoogle Scholar
Sies, H, Stahl, W & Sundquist, AR (1992) Antioxidant functions of vitamins. Vitamins E and C, beta-carotene and other carotenoids. Ann NY Acad Sci 669, 7–20.CrossRefGoogle Scholar
Steinberg, D (2000) Is there a potential therapeutic role for vitamin E or other antioxidants in atherosclerosis?. Curr Opin Lipidol 11, 603–607.CrossRefGoogle ScholarPubMed
Steinberg, D (1992) Antioxidants in prevention of human atherosclerosis. Summary of the proceedings of a National Heart, Lung and Blood Institute Workshop, September 5–6, 1991, Bethesda, Maryland. Circulation 85, 2337–2344.CrossRefGoogle ScholarPubMed
Steinberg, D & Witztum, JL (2002) Is the oxidative modification hypothesis relevant to human atherosclerosis?, Do the antioxidant trials conducted to date refute the hypothesis?. Circulation 105, 2107–2111.CrossRefGoogle ScholarPubMed
Stephens, NG, Parsons, A, Schofield, PM, Kelly, F, Cheeseman, K & Mitchinson, MJ (1996) Randomized controlled trial of vitamin E in patients with coronary disease: Cambridge Heart Antioxidant Study (CHAOS). Lancet 347, 781–786.CrossRefGoogle ScholarPubMed
Stocker, R (1999) Dietary and pharmacological antioxidants in atherosclerosis. Curr Opin Lipidol 10, 589–597.CrossRefGoogle ScholarPubMed
Takeya, M, Yoshimura, T, Leonharf, EJ & Takahashi, K (1993) Detection of monocyte chemoattractant protein-1 in human atherosclerotic lesions by an anti-monocyte chemoattractant protein-1antibody. Hum Pathol 24, 534–539.CrossRefGoogle Scholar
Tangirala, RK, Rubin, EM & Palinski, W (1995) Quantification of atherosclerosis in murine models: correlation between lesions in the aortic origin and in the entire aorta, and differences in the extent of lesions between sexes in LDL receptor-deficient and apolipoprotein-E deficient mice. J Lipid Res 36, 2320–2328.CrossRefGoogle Scholar
Terasawa, Y, Ladha, Z, Leonard, SW, et al. (2000) Increased atherosclerosis in hyperlipidemic mice deficient in α-tocopherol transfer protein and vitamin E. Proc Natl Acad Sci USA 97, 13830–13834.CrossRefGoogle ScholarPubMed
The Heart Outcomes Prevention Evaluation Study Investigators (2000) Vitamin E supplementation and cardiovascular events in high-risk patients. New Eng J Med 342, 154–160.CrossRefGoogle Scholar
Tsimikas, S, Shortal, BP, Witztum, JL & Palinski, W (2000) In vivo uptake of radiolabeled MDA, an oxidation-specific monoclonal antibody, provides an accurate measure of atherosclerotic lesions to their regression. Arterioscler Thromb Vasc Biol 20, 689–697.CrossRefGoogle Scholar
Ueda, T & Igarashi, O (1990) Determination of vitamin E in biological specimens and foods by HPLC-pretreatment of samples and extraction of tocopherols. J Micronutr Anal 7, 79–96.Google Scholar
Upston, JM, Terentis, AC, Morris, K, Keaney, JF Jr & Stocker, R (2002) Oxidized lipid accumulates in the presence of alpha-tocopherol in atherosclerosis. Biochem J 363, 753–760.CrossRefGoogle ScholarPubMed
Virmani, R, Kolodgie, FD, Burke, AP, Farb, A & Schwartz, SM (2000) Lessons from sudden coronary death. A comprehensive morphological classification scheme for atherosclerotic lesions. Arterioscler Thromb Vasc Biol 20, 1262–1275.CrossRefGoogle Scholar
Wefers, H & Sies, H (1988) The protection by ascorbate and glutathione against microsomal lipid peroxidation is dependent on vitamin E. FEBS Lett 174, 353–357.Google ScholarPubMed
Williams, RJ, Motteram, JM, Sharp, CH & Gallagher, PJ (1992) Dietary vitamin E and the attenuation of early lesion development in modified Watanabe rabbits. Atherosclerosis 94, 153–159.CrossRefGoogle ScholarPubMed
Witztum, JL & Steinberg, D (2001) The oxidative modification hypothesis of atherosclerosis: does it hold for humans?. Trends Cardiovasc Med 11, 93–102.CrossRefGoogle ScholarPubMed
Wu, D, Koga, T, Martin, KR & Meydani, M (1999) Effect of vitamin E on human aortic endothelial cell production of chemokines and adhesion to monocytes. Atherosclerosis 147, 297–307.CrossRefGoogle Scholar