Recent advances in lipoprotein and atherosclerosis: A nutrigenomic approach


  • Sergio López Grupo de Nutrición Celular y Molecular, Instituto de la Grasa, CSIC
  • Almudena Ortega Grupo de Nutrición Celular y Molecular, Instituto de la Grasa, CSIC
  • Lourdes Varela Grupo de Nutrición Celular y Molecular, Instituto de la Grasa, CSIC
  • Beatriz Bermúdez Grupo de Nutrición Celular y Molecular, Instituto de la Grasa, CSIC
  • Francisco JG Muriana Grupo de Nutrición Celular y Molecular, Instituto de la Grasa, CSIC
  • Rocío Abia Grupo de Nutrición Celular y Molecular, Instituto de la Grasa, CSIC



Atherosclerosis, Diet, Lipoproteins, Nutrigenomics, Postprandial state, Vascular cells


Atherosclerosis is a disease in which multiple factors contribute to the degeneration of the vascular wall. Many risk factors have been identified as having influence on the progression of atherosclerosis among them, the type of diet. Multifactorial interaction among lipoproteins, vascular wall cells, and inflammatory mediators has been recognised as the basis of atherogenesis. Dietary intake affects lipoprotein concentration and composition providing risk or protection at several stages of atherosclerosis. More intriguingly, it has been demonstrated that the extent to which each lipid or lipoprotein is associated with cardiovascular disease depends on the time to last meal; thus, postprandial lipoproteins, main lipoproteins in blood after a high-fat meal, have been shown to strongly influence atherogenesis. As a complex biological process, the full cellular and molecular characterization of atherosclerosis derived by diet, calls for application of the newly developing “omics” techniques of analysis. This review will considered recent studies using high-throughput technologies and a nutrigenomic approach to reveal the patho-physiological effects that the fasting and postprandial lipoproteins may exert on the vascular wall.


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Abia R, Pacheco YM, Perona JS, Montero E, Muriana FJ, Ruiz-Gutiérrez V. 2001. The metabolic availability of dietary triacylglycerols from two high oleic oils during the postprandial period does not depend on the amount of oleic acid ingested by healthy men. J Nutr. 131, 59-65.

Alipour A, van Oostrom AJ, Izraeljan A, Verseyden C, Collins JM, Frayn KN, Plokker TW, Elte JW, Castro Cabezas M. 2008. Leukocyte activation by triglyceride-rich lipoproteins. Arterioscler. Thromb. Vasc. Biol. 28, 792-797. doi:10.1161/ATVBAHA.107.159749

Arab L. 2004. Individualized nutritional recommendations: do we have the measurements needed to assess risk and make dietary recommendations? Proc. Nutr. Soc. 63, 167-172. doi:10.1079/PNS2003325 PMid:15070447

Aramaki Y, Mitsuoka H, Toyohara M, Jinnai T, Kanatani K, Nakajima K, Mukai E, Yamada Y, Kita T, Inagaki N, Kume N. 2008. Lectin-like oxidized LDL receptor-1 (LOX-1) acts as a receptor for remnant-like lipoprotein particles (RLPs) and mediates RLP-induced migration of vascular smooth muscle cells. Atherosclerosis 198, 272-279. doi:10.1016/j.atherosclerosis.2007.12.017 PMid:18282574

Armah CK, Jackson KG, Doman I, James L, Cheghani F, Minihane AM. 2008. Fish oil fatty acids improve postprandial vascular reactivity in healthy men. Clin. Sci. (Lond), 114, 679-686. doi:10.1042/CS20070277 PMid:18052925

Bansal S, Buring JE, Rifai N, Mora S, Sacks FM, Ridker PM. 2007. Fasting compared with nonfasting triglycerides and risk of cardiovascular events in women. JAMA 298, 309-316. doi:10.1001/jama.298.3.309 PMid:17635891

Bermúdez B, López S, Pacheco YM, Villar J, Muriana FJ, Hoheisel JD, Bauer A, Abia R. 2008. Influence of postprandial triglyceride-rich lipoproteins on lipidmediated gene expression in smooth muscle cells of the human coronary artery. Cardiovasc. Res. 79, 294-303. doi:10.1093/cvr/cvn082 PMid:18359786

Berliner JA, Subbanagounder G, Leitinger N, Watson AD, Vora D. 2001. Evidence for a role of phospholipid oxidation products in atherogenesis. Trends Cardiovasc. Med. 11, 142-147. doi:10.1016/S1050-1738(01)00098-6 PMid:11686004

Bravo E, Napolitano M. 2007. Mechanisms involved in chylomicron remnant lipid uptake by macrophages. Biochem. Soc. Trans 35, 459-463. doi:10.1042/BST0350459 PMid:17511627

Chen CY, Lee CM, Hsu HC, Yang CY, Chow LP, Lee YT. 2007. Proteomic approach to study the effects of various oxidatively modified low-density lipoprotein on regulation of protein expression in human umbilical vein endothelial cell. Life Sci.80, 2469-2480. doi:10.1016/j.lfs.2007.04.007 PMid:17509619

Cohn JS. 2006. Postprandial lipemia and remnant lipoproteins. Clin. Lab. Med. 26, 773-786. doi:10.1016/j.cll.2006.07.003 PMid:17110239

Dupont A, Chwastyniak M, Beseme O, Guihot AL, Drobecq H, Amouyel P, Pinet F. 2008. Application of saturation dye 2D-DIGE proteomics to characterize proteins modulated by oxidized low density lipoprotein treatment of human macrophages. J. Proteome Res. 7, 3572-3582. doi:10.1021/pr700683s PMid:18549265

Fach EM, Garulacan LA, Gao J, Xiao Q, Storm SM, Dubaquie YP, Hefta SA, Opiteck GJ. 2004. In vitro biomarker discovery for atherosclerosis by proteomics. Mol. Cell. Proteomics 3, 1200-1210. doi:10.1074/mcp.M400160-MCP200

Fitó M, Guxens M, Corella D, Sáez G, Estruch R, de la Torre R, Francés F, Cabezas C, López-Sabater Mdel C, Marrugat J, García-Arellano A, Arós F, Ruiz-Gutierrez V, Ros E, Salas-Salvadó J, Fiol M, Solá R, Covas MI; for the PREDIMED Study Investigators. 2007. Effect of a traditional Mediterranean diet on lipoprotein oxidation: a randomized controlled trial. Arch. Intern. Med. 167, 1195-1203. doi:10.1001/archinte.167.11.1195 PMid:17563030

Frostegård J. 2005. Atherosclerosis in patients with autoimmune disorders. Arterioscler. Thromb. Vasc. Biol. 25, 1776-1785. doi:10.1161/

Furtado JD, Campos H, Appel LJ, Miller ER, Laranjo N, Carey VJ, Sacks FM. 2008. Effect of protein, unsaturated fat, and carbohydrate intakes on plasma apolipoprotein B and VLDL and LDL containing apolipoprotein C-III: results from the OmniHeart Trial. Am. J. Clin. Nutr. 87, 1623-1630.

Galle J, Hansen-Hagge T, Wanner C, Seibold S. 2006. Impact of oxidized low density lipoprotein on vascular cells. Atherosclerosis 185, 219-226. doi:10.1016/j.atherosclerosis.2005.10.005 PMid:16288760

Gargalovic PS, Imura M, Zhang B, Gharavi NM, Clark MJ, Pagnon J, Yang WP, He A, Truong A, Patel S, Nelson SF, Horvath S, Berliner JA, Kirchgessner TG, Lusis AJ. 2006. Identification of inflammatory gene modules based on variations of human endothelial cell responses to oxidized lipids. Proc. Natl. Acad. Sci.U S A 103, 12741-12746. doi:10.1073/pnas.0605457103

Gharavi NM, Gargalovic PS, Chang I, Araujo JA, Clark MJ, Szeto WL, Watson AD, Lusis AJ, Berliner JA. 2007. High-density lipoprotein modulates oxidized phospholipid signaling in human endothelial cells from proinflammatory to anti-inflammatory. Arterioscler. Thromb. Vasc. Biol. 27, 1346-53. doi:10.1161/ATVBAHA.107.141283

Hammad SM, Twal WO, Barth JL, Smith KJ, Saad AF, Virella G, Scott Argraves W, Lopes-Virella MF. 2008. Oxidized LDL immune complexes and oxidized LDL differentially affect the expression of genes involved with inflammation and survival in human U937 monocytic cells. Atherosclerosis (Epub ahead of print) doi:10.1016/j.atherosclerosis.2008.05.032 PMid:18597759

Hilpert KF, West SG, Kris-Etherton PM, Hecker KD, Simpson NM, Alaupovic P. 2007. Postprandial effect of n-3 polyunsaturated fatty acids on apolipoprotein Bcontaining lipoproteins and vascular reactivity in type 2 diabetes. Am. J. Clin. Nutr. 85, 369-376.

Hurtado I, Fiol C, Gracia V, Caldú P. 1996. In vitro oxidised HDL exerts a cytotoxic effect on macrophages. Atherosclerosis 125, 39-46. doi:10.1016/0021-9150(96)05840-6 PMid:8831925

Jagla A, Schrezenmeir J. 2001. Postprandial triglycerides and endothelial function. Exp. Clin. Endocrinol. Diabetes 109, S533-547. doi:10.1055/s-2001-15116

Kawakami A, Tanaka A, Chiba T, Nakajima K, Shimokado K, Yoshida M. 2003. Remnant lipoprotein-induced smooth muscle cell proliferation involves epidermal growth factor receptor transactivation. Circulation 108, 2679-2688. doi:10.1161/01.CIR.0000093278.75565.87 PMid:14623816

Kawakami A, Yoshida M. 2005. Remnant lipoproteins and atherogenesis. J. Atheroscler. Thromb. 12, 73-76.

Kinumi T, Ogawa Y, Kimata J, Saito Y, Yoshida Y, Niki E. 2005. Proteomic characterization of oxidative dysfunction in human umbilical vein endothelial cells (HUVEC) induced by exposure to oxidized LDL. Free Radic. Res. 39, 1335-1344. doi:10.1080/10715760500306695 PMid:16298863

Kita T, Kume N, Minami M, Hayashida K, Murayama T, Sano H, Moriwaki H, Kataoka H, Nishi E, Horiuchi H, Arai H, Yokode M. 2001. Role of oxidized LDL in atherosclerosis. Ann. N. Y. Acad. Sci. 947, 199-205.

Lopez-Miranda J, Williams C, Lairon D. 2007. Dietary, physiological, genetic and pathological influences on postprandial lipid metabolism. Br. J. Nutr. 98,458-473. doi:10.1017/S000711450774268X PMid:17705891

Levula M, Jaakkola O, Luomala M, Nikkari ST, Lehtimäki T. 2006. Effects of oxidized low- and high-density lipoproteins on gene expression of human macrophages. Scand. J. Clin. Lab. Invest.66, 497-508. doi:10.1080/00365510600836651 PMid:17000557

Mikita T, Porter G, Lawn RM, Shiffman D. 2001. Oxidized low density lipoprotein exposure alters the transcriptional response of macrophages to inflammatory stimulus. J. Biol. Chem. 276, 45729-45739. doi:10.1074/jbc.M106114200 PMid:11577090

Mora S, Rifai N, Buring JE, Ridker PM. 2008. Fasting compared with nonfasting lipids and apolipoproteins for predicting incident cardiovascular events. Circulation 118, 993-1001. doi:10.1161/CIRCULATIONAHA.108.777334 PMid:18711012

Nakamura T, Takano H, Umetani K, Kawabata K, Obata JE, Kitta Y, Kodama Y, Mende A, Ichigi Y, Fujioka D, Saito Y, Kugiyama K. 2005. Remnant lipoproteinemia is a risk factor for endothelial vasomotor dysfunction and coronary artery disease in metabolic syndrome. Atherosclerosis 181, 321-327. doi:10.1016/j.atherosclerosis.2005.01.012 PMid:16039286

Nicholls SJ, Lundman P, Harmer JA, Cutri B, Griffiths KA, Rye KA, Barter PJ, Celermajer DS. 2006. Consumption of saturated fat impairs the antiinflammatory properties of high-density lipoproteins and endothelial function. J. Am. Coll. Cardiol. 48, 715-720. doi:10.1016/j.jacc.2006.04.080 PMid:16904539

Nordestgaard BG, Benn M, Schnohr P, Tybjaerg-Hansen A. 2007. Nonfasting triglycerides and risk of myocardial infarction, ischemic heart disease, and death in men and women. JAMA 298, 299-308. doi:10.1001/jama.298.3.299 PMid:17635890

Norata GD, Grigore L, Raselli S, Redaelli L, Hamsten A, Maggi F, Eriksson P, Catapano AL. 2007. Post-prandial endothelial dysfunction in hypertriglyceridemic subjects: molecular mechanisms and gene expression studies. Atherosclerosis 193, 321-327. doi:10.1016/j.atherosclerosis.2006.09.015 PMid:17055512

Norata GD, Grigore L, Raselli S, Seccomandi PM, Hamsten A, Maggi FM, Eriksson P, Catapano AL. 2006. Triglyceride-rich lipoproteins from hypertriglyceridemic subjects induce a pro-inflammatory response in the endothelium: Molecular mechanisms and gene expression studies. J. Mol. Cell. Cardiol. 40, 484-494. doi:10.1016/j.yjmcc.2006.01.022 PMid:16516917

Norata GD, Pirillo A, Callegari E, Hamsten A, Catapano AL, Eriksson P. 2003. Gene expression and intracellular pathways involved in endothelial dysfunction induced by VLDL and oxidised VLDL. Cardiovasc. Res. 59, 169-180. doi:10.1016/S0008-6363(03)00335-3 PMid:12829188

Pacheco YM, Abia R, Perona JS, Meier KE, Montero E, Ruiz-Gutiérrez V, Muriana FJ. 2002. Triacylglycerolrich lipoproteins trigger the phosphorylation of extracellular-signal regulated kinases in vascular cells. Life Sci. 71, 1351-1360. doi:10.1016/S0024-3205(02)01860-X PMid:12127156

Padró T, Peña E, García-Arguinzonis M, Llorente-Cortes V, Badimon L. 2008. Low-density lipoproteins impair migration of human coronary vascular smooth muscle cells and induce changes in the proteomic profile of myosin light chain. Cardiovasc. Res. 77, 211-220. doi:10.1093/cvr/cvm045 PMid:18006454

Rapp JH, Lespine A, Hamilton RL, Colyvas N, Chaumeton AH, Tweedie-Hardman J, Kotite L, Kunitake ST, Havel RJ, Kane JP. 1994. Triglyceriderich lipoproteins isolated by selected-affinity antiapolipoprotein B immunosorption from human atherosclerotic plaque. Arterioscler. Thromb. 14, 1767-1774.

Reeve JL, Stenson-Cox C, O’Doherty A, Pörn-Ares I, Ares M, O’Brien T, Samali A. 2007. OxLDL-induced gene expression patterns in CASMC are mimicked in apoE-/- mice aortas. Biochem. Biophys. Res. Commun. 356, 681-686. doi:10.1016/j.bbrc.2007.03.027 PMid:17374365

Saad AF, Virella G, Chassereau C, Boackle RJ, Lopes-Virella MF. 2006. OxLDL immune complexes activate complement and induce cytokine production by MonoMac 6 cells and human macrophages. J. Lipid. Res. 47, 1975-1983. doi:10.1194/jlr.M600064-JLR200

Subbiah MT. 2008. Understanding the nutrigenomic definitions and concepts at the food-genome junction. OMICS 12, (Epub ahead of print)

Sukhanov S, Delafontaine P. 2005. Protein chip-based microarray profiling of oxidized low density lipoprotein-treated cells. Proteomics 5, 1274-1280. doi:10.1002/pmic.200400985 PMid:15732133

Sukhanov S, Hua Song Y, Delafontaine P. 2003. Global analysis of differentially expressed genes in oxidized LDL-treated human aortic smooth muscle cells. Biochem. Biophys. Res. Commun. 306, 443-449. doi:10.1016/S0006-291X(03)00990-2 PMid:12804583

Tall AR. 2008. Cholesterol efflux pathways and other potential mechanisms involved in the atheroprotective effect of high density lipoproteins. J. Intern. Med. 263, 256-273. doi:10.1111/j.1365-2796.2007.01898.x PMid:18271871

Thompson SM, Arrowsmith FE, Allen JR. 2003. Dietary management of galactosemia. Southeast Asian J. Trop. Med. Public. Health 34, 212-214.

Tsimikas S, Brilakis ES, Miller ER, McConnell JP, Lennon RJ, Kornman KS, Witztum JL, Berger PB. 2005. Oxidized phospholipids, Lp(a) lipoprotein, and coronary artery disease. N. Engl. J. Med. 353, 46-57. doi:10.1056/NEJMoa043175 PMid:16000355

Tsimikas S, Kiechl S, Willeit J, Mayr M, Miller ER, Kronenberg F, Xu Q, Bergmark C, Weger S, Oberhollenzer F, Witztum JL. 2006. Oxidised phospholipids predict the presence and progression of carotid and femoral atherosclerosis and symptomatic cardiovascular disease: five-year prospective results from the Bruneck study. J. Am. Col. Cardiol. 47, 2219–2228. doi:10.1016/j.jacc.2006.03.001 PMid:16750687

Valiyaveettil M, Kar N, Ashraf MZ, Byzova TV, Febbraio M, Podrez EA. 2008. Oxidized high-density lipoprotein inhibits platelet activation and aggregation via scavenger receptor BI. Blood 111, 1962-1971. doi:10.1182/blood-2007-08-107813 PMid:17993610

van Spronsen FJ, van Rijn M, Bekhof J, Koch R, Smit PG. 2001. Phenylketonuria: tyrosine supplementation in phenylalanine-restricted diets. Am. J. Clin. Nutr.73, 153-157.

Virgili F, Ambra R, Muratori F, Natella F, Majewicz J, Minihane AM, Rimbach G. 2003. Effect of oxidized low-density lipoprotein on differential gene expression in primary human endothelial cells. Antioxid. Redox Signal 5, 237-247. doi:10.1089/152308603764816596 PMid:12716483

Williams CM, Maitin V, Jackson KG. 2004. Triacylglycerolrich lipoprotein-gene interactions in endothelial cells. Biochem. Soc. Trans 32, 994-998. doi:10.1042/BST0320994 PMid:15506945

Yang PY, Rui YC, Yang PY, Yu YL. 2007. Proteomic analysis of foam cells. Methods Mol. Biol. 357, 297-305.

Yu YL, Huang ZY, Yang PY, Rui YC, Yang PY. 2003. Proteomic studies of macrophage-derived foam cell from human U937 cell line using two-dimensional gel electrophoresis and tandem mass spectrometry. J. Cardiovasc. Pharmacol. 42, 782-789. doi:10.1097/00005344-200312000-00013 PMid:14639101




How to Cite

López S, Ortega A, Varela L, Bermúdez B, Muriana FJ, Abia R. Recent advances in lipoprotein and atherosclerosis: A nutrigenomic approach. grasasaceites [Internet]. 2009Mar.30 [cited 2022Dec.7];60(1):33-40. Available from:




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