Role of electronegative LDL and its associated antibodies in the pathogenesis of atherosclerosis

Clinical Lipidology

Volumn 5, Issue 5, 2010, Pages 719-729

  Faulin, Tanize Do Espirito Santo ^a   Cavalcante, Marcela Frota ^a   Abdalla, Dulcineia Saes Parra ^a  

^a UNIVERSITY OF SÃO PAULO   (Brazil)

Author keywords

autoantibody; biomarker; cardiovascular disease; immunization; inflammation; minimally modified LDL; risk factor

Indexed keywords

AUTOANTIBODY; ELECTRONEGATIVE LOW DENSITY LIPOPROTEIN; LOW DENSITY LIPOPROTEIN; UNCLASSIFIED DRUG;

ADAPTIVE IMMUNITY; ANTIBODY PRODUCTION; ANTIGEN ANTIBODY COMPLEX; APOPTOSIS; ATHEROGENESIS; ATHEROSCLEROSIS; ATHEROSCLEROTIC PLAQUE; DISEASE COURSE; ENDOTHELIUM CELL; FOAM CELL; HUMAN; IMMUNIZATION; IMMUNOCOMPETENT CELL; INFLAMMATION; INNATE IMMUNITY; LEUKOCYTE; MACROPHAGE; NONHUMAN; PATHOGENESIS; PRIORITY JOURNAL; PROTEIN MODIFICATION; REVIEW;

EID: 78149459415     PISSN: 17460875     EISSN: None     Source Type: Journal    
DOI: 10.2217/clp.10.52     Document Type: Review

References (117)

1. Gersh BJ, Sliwa K, Mayosi BM, Yusuf S: Novel therapeutic concepts: the epidemic of cardiovascular disease in the developing world: global implications. Eur. Heart J. 31(6), 642-648 (2010).
2. Loscalzo J: Molecular Mechanisms of Atherosclerosis. Taylor & Francis, UK and NY, USA (2005).
3. Hansson GK, Libby P: The immune response in atherosclerosis: a double-edged sword. Nat. Ver. Immunol. 6(7), 508-519 (2006).
4. Halvorsen B, Otterdal K, Dahl TB et al.: Atherosclerotic plaque stability - what determines the fate of a plaque? Prog. Cardiovasc. Dis. 51(3), 183-194 (2008).
5. Insull W Jr: The pathology of atherosclerosis: plaque development and plaque responses to medical treatment. Am. J. Med. 122(1A), 3-14 (2009).
6. De Spirito M, Brunelli R, Mei G et al.: Low density lipoprotein aged in plasma forms clusters resembling subendothelial droplets: aggregation via surface sites. Biophys. J. 9(11), 4239-4247 (2006).
7. Tabas I, Williams KJ, Borén J: Subendothelial lipoprotein retention as the initiating process in atherosclerosis: update and therapeutic implications. Circulation 116(16), 1832-1844 (2007).
8. Prassl R, Laggner P: Molecular structure of low density lipoprotein: current status and future challenges. Eur. Biophys. J. 38(2), 145-158 (2009).
9. Hevonoja T, Pentikainen MO, Hyvonen MT, Kovanen PT, Ala-Korpela M: Structure of low density lipoprotein (LDL) particles: basis for understanding molecular changes in modified LDL. Biochim. Biophys. Acta 1488(3), 189-210 (2000).
10. Kovanen PT, Pentikäinen MO: Circulating lipoproteins as proinflammatory and anti-inflammatory particles in atherogenesis. Curr. Opin. Lipidol. 14(5), 411-419 (2003).
11. Faulin TES, Garcia MCC, Abdalla DSP: Recent advances on detection of modified forms of low-density lipoproteins. Recent Pat. Endoc. Metab. Imm. Drug Disc. 3, 28-34 (2009).
12. Tao JL, Ruan XZ, Li H et al.: Endoplasmic reticulum stress is involved in acetylated low-density lipoprotein induced apoptosis in THP-1 differentiated macrophages. Chin. Med. J. 122(15), 1794-1799 (2009).
13. Qin C, Nagao T, Grosheva I, Maxfield FR, Pierini LM: Elevated plasma membrane cholesterol content alters macrophage signaling and function. Arterioscler. Thromb. Vasc. Biol. 26(2), 372-378 (2006).
14. Parthasarathy S, Raghavamenon A, Garelnabi MO, Santanam N: Oxidized low-density lipoprotein. Methods Mol. Biol. 610, 403-417 (2010).
15. Sigala F, Kotsinas A, Savari P et al.: Oxidized LDL in human carotid plaques is related to symptomatic carotid disease and lesion instability. J. Vasc. Surg. 52(3), 704-713 (2010).
16. Holvoet P, Jenny NS, Schreiner PJ, Tracy RP, Jacobs DR: Multi-Ethnic Study of Atherosclerosis. The relationship between oxidized LDL and other cardiovascular risk factors and subclinical CVD in different ethnic groups: the Multi-Ethnic Study of Atherosclerosis (MESA). Atherosclerosis 194(1), 245-252 (2007).
17. Meisinger C, Baumert J, Khuseyinova N, Loewel H, Koenig W: Plasma oxidized low-density lipoprotein, a strong predictor for acute coronary heart disease events in apparently healthy, middle-aged men from the general population. Circulation 112(5), 651-657 (2005).
18. Uno M, Harada M, Takimoto O et al.: Elevation of plasma oxidized LDL in acute stroke patients is associated with ischemic lesions depicted by DWI and predictive of infarct enlargement. Neurol. Res. 27(1), 94-102 (2005).
19. Stocker R, Keaney JR: Role of oxidative modifications in atherosclerosis. Physiol. Rev. 84(4), 1381-1478 (2004).
20. Malle E, Marsche G, Arnhold J, Davies MJ: Modification of low-density lipoprotein by myeloperoxidase-derived oxidants and reagent hypochlorous acid. Biochim. Biophys. Acta 1761(4), 392-415 (2006).
21. Matsuura E, Hughes GR, Khamashta MA: Oxidation of LDL and its clinical implication. Autoimmun. Rev. 7(7), 558-566 (2008).
22. Annangudi SP, Deng Y, Gu X, Zhang W, Crabb JW, Salomon RG: Low-density lipoprotein has an enormous capacity to bind (E)-4-hydroxynon-2-enal (HNE): detection and characterization of lysyl and histidyl adducts containing multiple molecules of HNE. Chem. Res. Toxicol. 21(7), 1384-1395 (2008).
23. Leonarduzzi G, Chiarpotto E, Biasi F, Poli G: 4-hydroxynonenal and cholesterol oxidation products in atherosclerosis. Mol. Nutr. Food Res. 49(11), 1044-1049 (2005).
24. Viigimaa M, Abina J, Zemtsovskaya G et al.: Malondialdehyde-modified lowdensity lipoproteins as biomarker for atherosclerosis. Blood Press. 19(3), 164-168 (2010).
25. Asci G, Basci A, Shah SV et al.: Carbamylated low-density lipoprotein induces proliferation and increases adhesion molecule expression of human coronary artery smooth muscle cells. Nephrology 13(6), 480-486 (2008).
26. Shah SV, Apostolov EO, Ok E, Basnakian AG: Novel mechanisms in accelerated atherosclerosis in kidney disease. J. Ren. Nutr. 18(1), 65-69 (2008).
27. Ok E, Basnakian AG, Apostolov EO, Barri YM, Shah SV: Carbamylated lowdensity lipoprotein induces death of endothelial cells: a link to atherosclerosis in patients with kidney disease. Kidney Int. 68(1), 173-178 (2005).
28. Wang Z, Nicholls SJ, Rodriguez ER et al.: Protein carbamylation links inflammation, smoking, uremia and atherogenesis. Nat. Med. 13(10), 1176-1184 (2007).
29. Brown BE, Rashid I, Van Reyk DM, Davies MJ: Glycation of low-density lipoprotein results in the time-dependent accumulation of cholesteryl esters and apolipoprotein B-100 protein in primary human monocyte-derived macrophages. FEBS J. 274(6), 1530-1541 (2007).
30. Younis N, Sharma R, Soran H, Charlton-Menys V, Elseweidy M, Durrington PN: Glycation as an atherogenic modification of LDL. Curr. Opin. Lipidol. 19(4), 378-384 (2008).
31. Basta G, Schmidt AM, De Caterina R: Advanced glycation end products and vascular inflammation: implications for accelerated atherosclerosis in diabetes. Cardiovasc. Res. 63(4), 582-592 (2004). (Pubitemid 39078671)
32. Hodgkinson CP, Laxton RC, Patel K, Ye S: Advanced glycation end-product of low density lipoprotein activates the Toll-like 4 receptor pathway implications for diabetic atherosclerosis. Arterioscler. Thromb. Vasc. Biol. 28(12), 2275-2281 (2008).
33. Avogaro P, Bittolon-Bon G, Cazzolato G: Presence of a modified low density lipoprotein in humans. Arteriosclerosis 8(1), 79-87(1988).
34. Yang CY, Raya JL, Chen HH et al.: Isolation, characterization, and functional assessment of oxidatively modified subfractions of circulating low-density lipoproteins. Arterioscler. Thromb. Vasc. Biol. 23(6), 1083-1090 (2003).
35. Abe Y, Fornage M, Yang CY et al.: L5, the most electronegative subfraction of plasma LDL, induces endothelial vascular cell adhesion molecule 1 and CXC chemokines, which mediate mononuclear leukocyte adhesion. Atherosclerosis 192(1), 56-66 (2007).
36. Harkewicz R, Hartvigsen K, Almazan F, Dennis EA, Witztum JL, Miller YI: Cholesteryl ester hydroperoxides are biologically active components of minimally oxidized low density lipoprotein. J. Biol. Chem. 283(16), 10241-10251 (2008).
37. Benz DJ, Mol M, Ezaki M et al.: Enhanced levels of lipoperoxides in low density lipoprotein incubated with murine fibroblast expressing high levels of human 15-lipoxygenase. J. Biol. Chem. 270(10), 5191-5197 (1995).
38. Ezaki M, Witztum JL, Steinberg D: Lipoperoxides in LDL incubated with fibroblasts that overexpress 15-lipoxygenase. J. Lipid Res. 36(9), 1996-2004 (1995).
39. Levitan I, Volkov S, Subbaiah PV: Oxidized LDL: diversity, patterns of recognition, and pathophysiology. Antioxid. Redox Signal. 13(1), 39-75 (2010).
40. Sanchez-Quesada JL, Benitez S, Ordóñez-Llanos J: Electronegative lowdensity lipoprotein. Curr. Opin. Lipidol. 15(3), 329-335 (2004).
41. Fabjan JS, Abuja PM, Schaur RJ, Sevanian A: Hypochlorite induces the formation of LDL(-), a potentially atherogenic low density lipoprotein subspecies. FEBS Lett. 499, 69-72 (2001).
42. Asatryan L, Hamilton RT, Isas JM, Hwang J, Kayed R, Sevanian A: LDL phospholipid hydrolysis produces modified electronegative particles with an unfolded apoB-100 protein. J. Lipid Res. 46(1), 115-122 (2005).
43. Greco G, Balogh G, Brunelli R et al.: Generation in human plasma of misfolded, aggregation-prone electronegative low density lipoprotein. Biophys. J. 97(2), 628-635 (2009).
44. De Castellarnau, C, Sanchez-Quesada JL, Benítez S: Electronegative LDL from normolipemic subjects induces IL-8 and monocyte chemotactic protein secretion by human endothelial cells. Arterioscler. Thromb. Vasc. Biol. 20(10), 2281-2287 (2000).
45. Faulin TES, Sena KCM, Telles ERA, Grosso DM, Faulin EJB, Abdalla DSP: Validation of a novel ELISA for measurement of Electronegative LDL. Clin. Chem. Lab. Med. 46(12), 1769-1775 (2008).
46. Damasceno NR, Sevanian A, Apolinario E, Oliveira JM, Fernandes I, Abdalla DSP: Detection of electronegative low density lipoprotein (LDL-) in plasma and atherosclerotic lesions by monoclonal antibody-based immunoassays. Clin. Biochem. 39(1), 28-38 (2006).
47. Benítez S, Ordóñez-Llanos J, Franco M et al.: Effect of simvastatin in familial hypercholesterolemia on the affinity of electronegative low-density lipoprotein subfractions to the low-density lipoprotein receptor. Am. J. Cardiol. 93(4), 414-420 (2004).
48. Sánchez-Quesada JL, Otal-Entraigas C, Franco M et al.: Effect of simvastatin treatment on the electronegative low-density lipoprotein present in patients with heterozygous familial hypercholesterolemia. Am. J. Cardiol. 84(6), 655-659 (1999).
49. Queiroz Mello AP, Silva IT, Oliveira AS et al.: Electronegative low-density lipoprotein is associated with dense low-density lipoprotein in subjects with different levels of cardiovascular risk. Lipids 45(7), 619-625 (2010).
50. Moro E, Zambon C, Pianetti S, Cazzolato G, Pais M, Bittolo Bon G: Electronegative low density lipoprotein subform (LDL-) is increased in Type 2 (non-insulin-dependent) microalbuminuric diabetic patients and is closely associated with LDL susceptibility to oxidation. Acta Diabetol. 35(3), 161-164 (1998).
51. Sánchez-Quesada JL, Pérez A, Caixàs A et al.: Effect of glycemic optimization on electronegative low-density lipoprotein in diabetes: relation to nonenzymatic glycosylation and oxidative modification. J. Clin. Endocrinol. Metab. 86(7), 3243-3249 (2001).
52. Apolinário E, Ferderbar S, Pereira EC et al.: Minimally modified (electronegative) LDL(-) and anti-LDL(-) autoantibodies in diabetes mellitus and impaired glucose tolerance. Int. J. Atheroscler. 1(1), 42-47 (2006).
53. Ziouzenkova O, Asatryan L, Akmal M et al.: Oxidative cross-linking of apoB100 and hemoglobin results in low density lipoprotein modification in blood. Relevance to atherogenesis caused by hemodialysis. J. Biol. Chem. 274(27), 18916-18924 (1999).
54. Lobo J, Santos F, Grosso D et al.: Electronegative LDL and lipid abnormalities in patients undergoing hemodialysis and peritoneal dialysis. Nephron Clin. Pract. 108(4), 298-304 (2008).
55. Tomasik A, Jacheć W, Skrzep-Poloczek B, Widera-Romuk E, Wodniecki J, Wojciechowska C: Circulating electronegatively charged low-density lipoprotein in patients with angiographically documented coronary artery disease. Scand. J. Clin. Lab. Invest. 63(4), 259-265 (2003).
56. Oliveira JA, Sevanian A, Rodrigues RJ, Apolinario E, Abdalla DSP: Minimally modified electronegative LDL and its autoantibodies in acute and chronic coronary syndromes. Clin. Biochem. 39(7), 708-714 (2006).
57. Benítez S, Sanchez-Quesada JL, Lucero L et al.: Changes in low-density lipoprotein electronegativity and oxidizability after aerobic exercise are related to the increase in associated non-esterified fatty acids. Atherosclerosis 160(1), 223-232 (2002).
58. Benítez S, Villegas V, Bancells C et al.: Impaired binding affinity of electronegative low-density lipoprotein (LDL) to the LDL receptor is related to nonesterified fatty acids and lysophosphatidylcholine content. Biochemistry 43(50), 15863-15872 (2004).
59. Goldstein JL, Brown MS: The LDL receptor. Arterioscler. Thromb. Vasc. Biol. 29(4), 431-438 (2009).
60. Blanco FJ, Villegas S, Benítez S et al.: 2D-NMR reveals different populations of exposed lysine residues in the apoB-100 protein of electronegative and electropositive fractions of LDL particles. J. Lipid Res. 51(6), 1560-1565 (2010).
61. Esper RJ, Nordaby RA, Vilariño JO, Paragano A, Cacharrón JL, Machado RA: Endothelial dysfunction: a comprehensive appraisal. Cardiovasc. Diabetol. 5, 4 (2006).
62. Rodríguez G, Mago N, Rosa F: Role of inflammation in atherogenesis. Invest. Clin. 50(1), 109-129 (2009).
63. Benítez S, Camacho M, Bancells C, Vila L, Sanchez-Quesada JL, Ordóñez-Llanos J: Wide proinflammatory effect of electronegative low-density lipoprotein on human endothelial cells assayed by a protein array. Biochim. Biophys. Acta 1761(9), 1014-1021 (2006).
64. De Castellarnau C, Bancells C, Benitez S, Reina M, Ordóñez- Llanos J, Sanchez-Quesada JL: Atherogenic and inflammatory profile of human arterial endothelial cells (HUAEC) in response to LDL subfractions. Clin. Chim. Acta 376(1), 233-236 (2007).
65. Demuth K, Myara I, Chappey B et al.: A cytotoxic electronegative LDL subfraction is present in human plasma. Arterioscler. Thromb. Vasc. Biol. 16(6), 773-783 (1996).
66. Chen CH, Jiang T, Yang JH et al.: Low-density lipoprotein in hypercholesterolemic human plasma induces vascular endothelial cell apoptosis by inhibiting fibroblast growth factor 2 transcription. Circulation 107(16), 2102-2108 (2003).
67. Chen HH, Hosken BD, Huang M et al.: Electronegative LDLs from familial hypercholesterolemic patients are physicochemically heterogeneous but uniformly proapoptotic. J. Lipid Res. 48(1), 177-184 (2007).
68. Bancells C, Benítez S, Villegas S, Jorba O, Ordóñez- Llanos J, Sánchez-Quesada JL: Novel phospholipolytic activities associated with electronegative low-density lipoprotein are involved in increased self-aggregation. Biochemistry 47(31), 8186-8194 (2008).
69. Benitez S, Camacho M, Arcelus R et al.: Increased lysophosphatidylcholine and non-esterified fatty acid content in LDL induces chemokine release in endothelial cells - relationship with electronegative LDL. Atherosclerosis 177(2), 299-305 (2004).
70. Sanchez-Quesada JL, Benitez S, Perez A et al.: The inflammatory properties of electronegative low-density lipoprotein from Type 1 diabetic patients are related to increased platelet-activating factor acetylhydrolase activity. Diabetologia 48(10), 2162-2169 (2005).
71. Ziouzenkova O, Asatryan L, Sahady D et al.: Dual roles for lipolysis and oxidation in peroxisome proliferation-activator receptor responses to electronegative low density lipoprotein. J. Biol. Chem. 278(41), 39874-39881 (2003).
72. Benítez S, Bancells C, Ordóñez-Llanos J, Sánchez-Quesada JL: Pro-inflammatory action of LDL(-) on mononuclear cells is counteracted by increased IL10 production. Biochim. Biophys. Acta 1771(5), 613-622 (2007).
73. Shashkin P, Dragulev B, Ley K: Macrophage differentiation to foam cells. Curr. Pharm. Des. 11(23), 3061-3072 (2005).
74. Bobryshev YV: Monocyte recruitment and foam cell formation in atherosclerosis. Micron 37(3), 208-222 (2006).
75. Liu J, Thewke DP, Su YR, Linton MF, Fazio S, Sinensky MS: Reduced macrophage apoptosis is associated with accelerated atherosclerosis in low-density lipoprotein receptor-null mice. Arterioscler. Thromb. Vasc. Biol. 25(1), 174-179 (2005).
76. Tabas I: Consequences and therapeutic implications of macrophage apoptosis in atherosclerosis: the importance of lesion stage and phagocytic efficiency. Arterioscler. Thromb. Vasc. Biol. 25(11), 2255-2264 (2005).
77. Strasser A, Jost PJ, Nagata S: The many roles of FAS receptor signaling in the immune system. Immunity 30(2), 180-192 (2009).
78. Pedrosa AM, Faine LA, Grosso DM, De Las Heras B, Boscá L, Abdalla DSP: Electronegative LDL induction of apoptosis in macrophages: involvement of Nrf2. Biochim. Biophys. Acta 1801(4), 430-437 (2010).
79. Silverstein Rl: Inflammation, atherosclerosis, and arterial thrombosis: role of the scavenger receptor CD36. Cleve. Clin. J. Med. 76, 27-30 (2009).
80. Lundberg AM, Hansson GK: Innate immune signals in atherosclerosis. Clin. Immunol. 134(1), 5-24 (2010).
81. Andersson J, Libby P, Hansson GK: Adaptive immunity and atherosclerosis. Clin. Immunol. 134(1), 33-46 (2010).
82. Chou MY, Fogelstrand L, Hartvigsen K et al.: Oxidation-specific epitopes are dominant targets of innate natural antibodies in mice and humans. J. Clin. Invest. 119(5), 1335-1349 (2009).
83. Kunjathoor VV, Febbraio M, Podrez EA et al.: Scavenger receptors class A-I/II and CD36 are the principal receptors responsible for the uptake of modified low density lipoprotein leading to lipid loading in macrophages. J. Biol. Chem. 277(51), 49982-49988 (2002).
84. Ogura S, Kakino A, Sato Y et al.: LOX-1: multifunctional receptor underlying cardiovascular dysfunction. Circ. J. 73(11), 1993-1999 (2009).
85. Witztum JL: You are right too! J. Clin. Invest. 115(8), 2072-2075 (2005).
86. van Berkel TJ, Out R, Hoekstra M, Kuiper J, Biessen E, van Eck M: Scavenger receptors: friend or foe in atherosclerosis? Curr. Opin. Lipidol. 16(5), 525-535 (2005).
87. Yoshida H, Quehenberger O, Kondratenko N, Green S, Steinberg D: Minimally oxidized low-density lipoprotein increases expression of scavenger receptor A, CD36, and macrosialin in resident mouse peritoneal macrophages. Arterioscler. Thromb. Vasc. Biol. 18(5), 794-802 (1998).
88. Lu J, Yang JH, Burns AR et al.: Mediation of electronegative low-density lipoprotein signaling by LOX-1: a possible mechanism of endothelial apoptosis. Circ. Res. 104(5), 619-627 (2009).
89. Miller YI, Viriyakosol S, Binder CJ, Feramisco JR, Kirkland TN, Witztum JL: Minimally modified LDL binds to CD14, induces macrophage spreading via TLR4/MD-2, and inhibits phagocytosis of apoptotic cells. J. Biol. Chem. 278(3), 1561-1568 (2003).
90. Miller YI, Viriyakosol S, Worrall DS, Boullier A, Butler S, Witztum JL: Toll-like receptor 4-dependent and -independent cytokine secretion induced by minimally oxidized low-density lipoprotein in macrophages. Arterioscler. Thromb. Vasc. Biol. 25(6), 1213-1219 (2005).
91. Choi SH, Harkewicz R, Lee JH et al.: Lipoprotein accumulation in macrophages via Toll-like receptor-4-dependent fluid phase uptake. Circ. Res. 104(12), 1355-1363 (2009).
92. Mullick AE, Tobias OS, Curtiss LK: Toll-like receptors and atherosclerosis: key contributors in disease and health? Immunol. Res. 34(3), 193-209 (2006).
93. Miller YI: Toll-like receptors and atherosclerosis: oxidized LDL as an endogenous Toll-like receptor ligand. Future Cardiol. 1(6), 785-792 (2005).
94. Milioti N, Bermudez-Fajardo A, Penichet ML, Oviedo-Orta E: Antigeninduced immunomodulation in the pathogenesis of atherosclerosis. Clin. Dev. Immunol. 7, 235-239 (2008).
95. Virella G, Thorpe SR, Alderson NL: Definition of the immunogenic forms of modified human LDL recognized by human autoantibodies and by rabbit hyperimmune antibodies. J. Lipid. Res. 45(10), 1859-1867 (2004).
96. Mironova MA, Klein RL, Virella GT, Lopes-Virella MF: Anti-modified LDL antibodies, LDL-containing immune complexes, and susceptibility of LDL to in vitro oxidation in patients with Type 2 diabetes. Diabetes 49(6), 1033-1041 (2000).
97. Burut DF, Karim Y, Ferns GA: The role of immune complexes in atherogenesis. Angiology 61(7), 679-689 (2010).
98. Van Leeuwen M, Damoiseaux J, Duijvestijna A, Tervaert JW: The therapeutic potential of targeting B cells and anti-oxLDL antibodies in atherosclerosis. Autoimm. Rev. 9(1), 53-57 (2009).
99. Stoll G, Bendszus M: Inflammation and atherosclerosis: novel insights into plaque formation and destabilization. Stroke 37(7), 1923-1932 (2006).
100. Packard RR, Lichtman AH, Libby P: Innate and adaptive immunity in atherosclerosis. Semin. Immunopathol. 31(1), 5-22 (2009).
101. Siqueira AA, Osiro K, Hirai AT, Abdalla DSP, Ferreira SRG: Antibodies against charged subfractions of LDLs are associated with disturbed ankle-brachial index and cardiovascular risk factors in a Japanese-Brazilian population with high prevalence of dislipidemias. Int. J. Atheroscl. 2(1), 68-74 (2007).
102. Zhang B, Matsunaga A, Rainwater DL et al.: Effects of Rosuvastatin on Electronegative LDL as Characterized by Capillary Isotachophoresis: the ROSARY study. J. Lipid Res. 50(9), 1832-1841 (2008).
103. Zhang B, Miura S, Yanagi D et al.: Reduction of charge-modified LDL by statin therapy in patients with CHD or CHD risk factors and elevated LDL-C levels: the SPECIAL Study. Atherosclerosis 201(2), 353-359 (2008).
104. Mafra D, Santos FR, Lobo JC et al.: Alpha-tocopherol supplementation decreases electronegative low-density lipoprotein concentration [LDL(-)] in haemodialysis patients. Nephrol. Dial. Transplant. 24(5), 1587-1592 (2009).
105. Teixeira Damasceno NR, Apolinário E, Dias Flauzino F, Fernandes I, Abdalla DSP: Soy isoflavones reduce electronegative low-density lipoprotein (LDL(-)) and anti-LDL(-) autoantibodies in experimental atherosclerosis. Eur. J. Nutr. 46(3), 125-132 (2007).
106. Natella F, Fidale M, Tubaro F, Ursini F, Scaccini C: Selenium supplementation prevents the increase in atherogenic electronegative LDL (LDL minus) in the postprandial phase. Nutr. Metab. Cardiovasc. Dis. 17(9), 649-656 (2007).
107. Shi GP: Immunomodulation of vascular diseases: atherosclerosis and autoimmunity. Eur J. Vasc. Endovasc. Surg. 39(4), 485-494 (2010).
108. Hansson GK, Nilsson J: Vaccination against atherosclerosis? Induction of atheroprotective immunity. Semin. Immunopathol. 31(1), 95-101 (2009).
109. Van Puijvelde GH, Van ES T, Habets KL, Hauer AD, Van Berkel TJ, Kuiper J: A vaccine against atherosclerosis: myth or reality? Future Cardiol. 4(2), 125-133 (2008).
110. Asgary S, Saberi SA, Azampanah S: Effect of immunization against ox-LDL with two different antigens on formation and development of atherosclerosis. Lipids Health Dis. 24, 6-32 (2007).
111. Habets KL, Van Puijvelde GH, Van Duivenvoorde LM et al.: Vaccination using oxidized low-density lipoprotein-pulsed dendritic cells reduces atherosclerosis in LDL receptor-deficient mice. Cardiovasc. Res. 85(3), 622-630 (2010).
112. Chyu KY, Zhao X, Reyes OS et al.: Immunization using an Apo B-100 related epitope reduces atherosclerosis and plaque inflammation in hypercholesterolemic apo E (-/-) mice. Biochem. Biophys. Res. Commun. 338(4), 1982-1989 (2005).
113. Nilsson J, Fredrikson GN, Björkbacka H, Chyu KY, Shah PK: Vaccines modulating lipoprotein autoimmunity as a possible future therapy for cardiovascular disease. J. Intern. Med. 266 (3), 221-231 (2009).
114. De Carvalho JF, Pereira RM, Shoenfeld Y: Vaccination for atherosclerosis. Clin. Rev. Allergy Immunol. 38(2-3), 135-140 (2010).
115. Schiopu A, Bengtsson J, Söderberg I et al.: Recombinant human antibodies against aldehyde-modified apolipoprotein B-100 peptide sequences inhibit atherosclerosis. Circulation 110(14), 2047-2052 (2004).
116. Faria-Neto JR, Chyu KY, Li X et al.: Passive immunization with monoclonal IgM antibodies against phosphorylcholine reduces accelerated vein graft atherosclerosis in apolipoprotein E-null mice. Atherosclerosis 189(1), 83-90 (2006).
117. Grosso DM, Ferderbar S, Wanschel AC, Krieger MH, Higushi ML, Abdalla DSP: Antibodies against electronegative LDL inhibit atherosclerosis in LDLr- /- mice. Braz. J. Med. Biol. Res. 41(12), 1086-1092 (2008).