peroxidation and degradation of low density lipoprotein phospholipids. Proc Natl Acad Sci USA 1984; 81: 3883–3887. 3 Kodama T, Freeman M, Rohrer L, Zabrecky J, Matsudaira P, Krieger M. Type I macrophage scavenger receptor contains alpha-helical and collagen- like coiled coils. Nature 1990; 343: 531–535. 4 Greaves DR, Gordon S. Thematic review series: the immune system and atherogenesis. Recent insights into the biology of macrophage scavenger receptors. J Lipid Res 2005; 46: 11–20. 5 Kimura J, Nakagami K, Amanuma K, Ohkuma S, Yoshida Y, Takano T. Monoclonal antibodies recognizing lipid-laden cells and extracellular regions with lipid-deposits in atherosclerotic aorta. Virchows Arch A Pathol Anat Histopathol 1986; 410: 159–164. 6 Mori M, Itabe H, Takatoku K, et al. Presence of phospholipid-neutral lipid complex structures in atherosclerotic lesions as detected by a novel mono- clonal antibody. J Biol Chem 1999; 274: 24828–24837. 7 Itabe H, Jimi S, Kamimura S, et al. Appearance of cross linked proteins in human atheroma and rat pre-fibrotic liver detected by a new monoclonal antibody. Biochim Biophys Acta 1998; 1406: 28–39. 8 Itabe H, Takeshima E, Iwasaki H, et al. A monoclonal antibody against oxidized lipoprotein recognizes foam cells in atherosclerotic lesions. Com- plex formation of oxidized phosphatidylcholine and polypeptides. J Biol Chem 1994; 269: 15274–15279. 9 Itabe H, Yamamoto H, Imanaka T, et al. Oxidized phosphatidylcholines that modify proteins. Analysis by monoclonal antibody against oxidized low den- sity lipoprotein. J Biol Chem 1996; 271: 33208–33217. 10 Spiteller G. Peroxyl radicals: inductors of neurodegenerative and other in- flammatory diseases. Their origin and how they transform cholesterol, phos- pholipids, plasmalogens, polyunsaturated fatty acids, sugars, and proteins into deleterious products. Free Radic Biol Med 2006; 41: 362–387. 11 Ehara S, Ueda M, Naruko T, et al. Elevated levels of oxidized low density li- poprotein show a positive relationship with the severity of acute coronary syndromes. Circulation 2001; 103: 1955–1960. 12 Nishi K, Itabe H, Uno M, et al. Oxidized LDL in carotid plaques and plasma associates with plaque instability. Arterioscler Thromb Vasc Biol 2002; 22: 1649–1654. 13 Lougheed M, Moore ED, Scriven DR, Steinbrecher UP. Uptake of oxidized LDL by macrophages differs from that of acetyl LDL and leads to expansion of an acidic endolysosomal compartment. Arterioscler Thromb Vasc Biol 1999; 19: 1881–1890. 14 Itabe H, Suzuki K, Tsukamoto Y, et al. Lysosomal accumulation of oxidized phosphatidylcholine-apolipoprotein B complex in macrophages: intracellular fate of oxidized low density lipoprotein. Biochim Biophys Acta 2000; 1487: 233–245. 15 Itabe H, Yamamoto H, Imanaka T, et al. Sensitive detection of oxidatively modified low density lipoprotein using a monoclonal antibody. J Lipid Res 1996; 37: 45–53. 16 Uno M, Kitazato KT, Nishi K, Itabe H, Nagahiro S. Raised plasma oxidised LDL in acute cerebral infarction. J Neurol Neurosurg Psychiatry 2003; 74: 312–316. 17 Itabe H, Ueda M. Measurement of plasma oxidized low-density lipoprotein and its clinical implications. J Atheroscler Thromb 2007; 14: 1–11. 18 Naruko T, Ueda M, Ehara S, et al. Persistent high levels of plasma oxidized low-density lipoprotein after acute myocardial infarction predict stent restenosis. Arterioscler Thromb Vasc Biol 2006; 26: 877–883. 19 Itabe H. Oxidized low density lipoprotein: what is understood and what remains to be clarified. Biol Pharm Bull 2003; 26: 1–9. 20 Tsimikas S, Bergmark C, Beyer RW, et al. Temporal increases in plasma markers of oxidized low-density lipoprotein strongly reflect the presence of acute coronary syndromes. J Am Coll Cardiol 2003; 41: 360–370. 21 Tsimikas S, Lau HK, Han KR, et al. Percutaneous coronary intervention results in acute increases in oxidized phospholipids and lipoprotein(a): short- term and long-term immunologic responses to oxidized low-density lipo- protein. Circulation 2004; 109: 3164–3170. 22 Fang JC, Kinlay S, Behrendt D, et al. Circulating autoantibodies to oxidized LDL correlate with impaired coronary endothelial function after cardiac transplantation. Arterioscler Thromb Vasc Biol 2002; 22: 2044–2048. 23 Holvoet P, Van Cleemput J, Collen D, Vanhaecke J. Oxidized low density lipoprotein is a prognostic marker of transplant-associated coronary artery disease. Arterioscler Thromb Vasc Biol 2000; 20: 698–702. 24 Holvoet P, Donck J, Landeloos M, et al. Correlation between oxidized low density lipoproteins and von Willebrand factor chronic renal failure. Thromb Haemost 1996; 76: 663–669. H. Itabe 25 Braun S, Ndrepepa G, von Beckerath N, et al. Lack of association between circulating levels of plasma oxidized low-density lipoproteins and clinical outcome after coronary stenting. Am Heart J 2005; 150: 550–556. 26 Velican C, Velican D. The precursors of coronary atherosclerotic plaques in subjects up to 40 years old. Atherosclerosis 1980; 37: 33–46. 27 Meir KS, Leitersdorf E. Atherosclerosis in the apolipoprotein-E-deficient mouse: a decade of progress. Arterioscler Thromb Vasc Biol 2004; 24: 1006– 1014. 28 Kato R, Mori C, Kitazato K, et al. Transient increase in plasma oxidized LDL during the progression of atherosclerosis in apolipoprotein E knockout mice. Arterioscler Thromb Vasc Biol 2009; 29: 33–39. 29 Tsimikas S, Aikawa M, Miller FJ Jr., et al. Increased plasma oxidized phospholipids: apolipoprotein B-100 ratio with concomitant depletion of oxi- dized phospholipids from atherosclerotic lesions after dietary lipid-lowering: a potential biomarker of early atherosclerosis regression. Arterioscler Thromb Vasc Biol 2007; 27: 175–181. 30 Suzuki M, Kamei M, Itabe H, et al. Oxidized phospholipids in the macula increase with age and in eyes with age-related macular degeneration. Mol Vis 2007; 23: 772–778. 31 Akagi M, Kanata S, Mori S, Itabe H, Sawamura T, Hamanishi C. Possible involvement of the oxidized low-density lipoprotein/lectin-like oxidized low- density lipoprotein receptor-1 system in pathogenesis and progression of human osteoarthritis. Osteoarthritis Cartilage 2007; 15: 281–290. 32 Eto M, Yoshikawa H, Fujimura H, et al. The role of CD36 in peripheral nerve remyelination after crush injury. Eur J Neurosci 2003; 17: 2659–2666. 33 Dietrich T, Jimenez M, Krall Kaye EA, Vokonas PS, Garcia RI. Age- dependent associations between chronic periodontitis/edentulism and risk of coronary heart disease. Circulation 2008; 117: 1668–1674. 34 Tonetti MS, D’Aiuto F, Nibali L, et al. Treatment of periodontitis and endothelial function. N Engl J Med 2007; 356: 911–920. 35 Bahekar AA, Singh S, Saha S, Molnar J, Arora R. The prevalence and incidence of coronary heart disease is significantly increased in periodontitis: a meta-analysis. Am Heart J 2007; 154: 830–837. 36 Haraszthy VI, Zambon JJ, Trevisan M, Zeid M, Genco RJ. Identification of periodontal pathogens in atheromatous plaques. J Periodontol 2000; 71: 1554–1560. 37 Li L, Messas E, Batista EL Jr., Levine RA, Amar S. Porphyromonas gingiva- lis infection accelerates the progression of atherosclerosis in a heterozygous apolipoprotein E-deficient murine model. Circulation 2002; 105: 861–867. 38 Lalla E, Lamster IB, Hofmann MA, et al. Oral infection with a periodontal pathogen accelerates early atherosclerosis in apolipoprotein E-null mice. Arterioscler Thromb Vasc Biol 2003; 23: 1405–1411. 39 Delima AJ, van Dyke TE. Origin and function of the cellular components in gingival crevice fluid. Periodontol 2000 2003; 31: 55–76. 40 Pisano E, Cabras T, Montaldo C, et al. Peptides of human gingival crevicular fluid determined by HPLC-ESI-MS. Eur J Oral Sci 2005; 113: 462–468. 41 Sakiyama Y, Kato R, Inoue S, Suzuki K, Itabe H, Yamamoto M. Detection of oxidized low-density lipoproteins in gingival crevicular fluid from dental patients. J Periodontal Res 2010; 45: 216–222. 42 Augé N, Andriew N, Nègre-Salvayre A, Thiers JC, Levade T, Salvayre R. The sphingomyelin-ceramide signaling pathway is involved in oxidized low density lipoprotein-induces cell proliferation. J Biol Chem 1996; 271: 19251–19255. 43 Kusuhara M, Chait A, Cader A, Berk BC. Oxidized LDL stimulates mitogen- activated protein kinases in smooth muscle cells and macrophages. Arterioscler Thromb Vasc Biol 1997; 17: 141–148. 44 Hamilton TA, Major JA, Chisolm GM. The effects of oxidized low density lipoproteins on inducible mouse macrophage gene expression are gene and stimulus dependent. J Clin Invest 1995; 95: 2020–2027. 45 Lehr HA, Hübner C, Finckh B, et al. Role of leukotriens in leukocyte adhesion following systemic administration of oxidatively modified human low density lipoprotein in hamsters. J Clin Invest 1991; 88: 9–14. 46 Higashi Y, Peng T, Du J, et al. A redox-sensitive pathway mediates oxidized LDL-induced downregulation of insulin-like growth factor-1 receptor. J Lipid Res 2005; 46: 1266–1277. 47 Ishii H, Kizaki K, Horie S, Kazama M. Oxidized low density lipoprotein reduces thrombomodulin transcription in cultured human endothelial cells through degradation of the lipoprotein in lysosomes. J Biol Chem 1996; 271: 8458–8465. 48 Sata M, Walsh K. Endothelial cell apoptosis induced by oxidized LDL is associated with the down-regulation of the cellular caspase inhibitor FLIP. J Biol Chem 1998; 273: 33103–33106. J. Clin. Biochem. Nutr. | July 2012 | vol. 51 | no. 1 | 7 ©2012 JCBN