Skip to main content

Preparation of LDL , Oxidation , Methods of Detection, and Applications in Atherosclerosis Research

  • Protocol
  • First Online:
Atherosclerosis

Part of the book series: Methods in Molecular Biology ((MIMB,volume 2419))

Abstract

The concept of lipid peroxidation has been known for a long time. It is now well established that LDL plays a major role in atherosclerosis. Oxidized low-density lipoprotein (Ox-LDL) has been studied for over 35 years. Numerous pro- and anti-atherogenic properties have been attributed to Ox-LDL. Component composition of Ox-LDL is complex due to the influence of various factors, including the source, method of preparation, storage and use. Hence, it is very difficult to clearly define and characterize Ox-LDL. It contains unoxidized and oxidized fatty acid derivatives both in the ester and free forms, their decomposition products, cholesterol and its oxidized products, proteins with oxidized amino acids and cross-links, polypeptides with varying extents of covalent modification with lipid oxidation products and many others. The measurement of lipid oxidation has been a great boon, not only to the understanding of the process but also in providing numerous serendipitous discoveries and methodologies. In this chapter, we outline the methodologies for the preparation and testing of various lipoproteins for oxidation studies.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Protocol
USD 49.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 219.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 279.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 379.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Similar content being viewed by others

References

  1. Johnson DR, Decker EA (2015) The role of oxygen in lipid oxidation reactions: a review. Annu Rev Food Sci Technol 6:171–190. https://doi.org/10.1146/annurev-food-022814-015532

    Article  CAS  PubMed  Google Scholar 

  2. Ayala A, Muñoz MF, Argüelles S (2014) Lipid peroxidation: production, metabolism, and signaling mechanisms of malondialdehyde and 4-hydroxy-2-nonenal. Oxidative Med Cell Longev 2014:360438. https://doi.org/10.1155/2014/360438

    Article  CAS  Google Scholar 

  3. Ito J, Komuro M, Parida IS, Shimizu N, Kato S, Meguro Y, Ogura Y, Kuwahara S, Miyazawa T, Nakagawa K (2019) Evaluation of lipid oxidation mechanisms in beverages and cosmetics via analysis of lipid hydroperoxide isomers. Sci Rep 9(1):7387. https://doi.org/10.1038/s41598-019-43645-1

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Domínguez R, Pateiro M, Gagaoua M, Barba FJ, Zhang W, Lorenzo JM (2019) A comprehensive review on lipid oxidation in meat and meat products. Antioxidants (Basel) 8(10):429. https://doi.org/10.3390/antiox8100429

    Article  CAS  Google Scholar 

  5. Moreno-García A, Kun A, Calero O, Medina M, Calero M (2018) An overview of the role of lipofuscin in age-related neurodegeneration. Front Neurosci 12:464. https://doi.org/10.3389/fnins.2018.00464

    Article  PubMed  PubMed Central  Google Scholar 

  6. Gaschler MM, Stockwell BR (2017) Lipid peroxidation in cell death. Biochem Biophys Res Commun 482(3):419–425. https://doi.org/10.1016/j.bbrc.2016.10.086

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Raghavamenon A, Garelnabi M, Babu S, Aldrich A, Litvinov D, Parthasarathy S (2009) Alpha-tocopherol is ineffective in preventing the decomposition of preformed lipid peroxides and may promote the accumulation of toxic aldehydes: a potential explanation for the failure of antioxidants to affect human atherosclerosis. Antioxid Redox Signal 11(6):1237–1248. https://doi.org/10.1089/ars.2008.2248

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Phaniendra A, Jestadi DB, Periyasamy L (2015) Free radicals: properties, sources, targets, and their implication in various diseases. Indian J Clin Biochem 30(1):11–26. https://doi.org/10.1007/s12291-014-0446-0

    Article  CAS  PubMed  Google Scholar 

  9. Therond P (2006) Oxidative stress and damages to biomolecules (lipids, proteins, DNA). Ann Pharm Fr 64(6):383–389. https://doi.org/10.1016/s0003-4509(06)75333-0

    Article  CAS  PubMed  Google Scholar 

  10. Goto S, Radak Z (2013) Implications of oxidative damage to proteins and DNA in aging and its intervention by caloric restriction and exercise. J Sport Health Sci 2:75–80. https://doi.org/10.1016/j.jshs.2013.03.004

    Article  Google Scholar 

  11. Yang L, Mih N, Anand A, Park JH, Tan J, Yurkovich JT, Monk JM, Lloyd CJ, Sandberg TE, Seo SW, Kim D, Sastry AV, Phaneuf P, Gao Y, Broddrick JT, Chen K, Heckmann D, Szubin R, Hefner Y, Feist AM, Palsson BO (2019) Cellular responses to reactive oxygen species are predicted from molecular mechanisms. Proc Natl Acad Sci U S A 116(28):14368–14373. https://doi.org/10.1073/pnas.1905039116

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Sharma P, Jha AB, Dubey RS, Pessarakli M (2012) Reactive oxygen species, oxidative damage, and antioxidative defense mechanism in plants under stressful conditions. J Bot 2012:217037. https://doi.org/10.1155/2012/217037

    Article  CAS  Google Scholar 

  13. Linton MF, Yancey PG, Davies SS, Jerome WG, Linton EF, Song WL, Doran AC, Vickers KC (2000) The role of lipids and lipoproteins in atherosclerosis. In: Feingold KR, Anawalt B, Boyce A et al (eds) Endotext. MDText.com, Inc. Copyright © 2000–2020. MDText.com, Inc., South Dartmouth

  14. Borén J, Chapman MJ, Krauss RM, Packard CJ, Bentzon JF, Binder CJ, Daemen MJ, Demer LL, Hegele RA, Nicholls SJ, Nordestgaard BG, Watts GF, Bruckert E, Fazio S, Ference BA, Graham I, Horton JD, Landmesser U, Laufs U, Masana L, Pasterkamp G, Raal FJ, Ray KK, Schunkert H, Taskinen M-R, van de Sluis B, Wiklund O, Tokgozoglu L, Catapano AL, Ginsberg HN (2020) Low-density lipoproteins cause atherosclerotic cardiovascular disease: pathophysiological, genetic, and therapeutic insights: a consensus statement from the European Atherosclerosis Society Consensus Panel. Eur Heart J 41(24):2313–2330. https://doi.org/10.1093/eurheartj/ehz962

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Steinbrecher UP, Parthasarathy S, Leake DS, Witztum JL, Steinberg D (1984) Modification of low density lipoprotein by endothelial cells involves lipid peroxidation and degradation of low density lipoprotein phospholipids. Proc Natl Acad Sci U S A 81(12):3883–3887. https://doi.org/10.1073/pnas.81.12.3883

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Quinn MT, Parthasarathy S, Fong LG, Steinberg D (1987) Oxidatively modified low density lipoproteins: a potential role in recruitment and retention of monocyte/macrophages during atherogenesis. Proc Natl Acad Sci U S A 84(9):2995–2998. https://doi.org/10.1073/pnas.84.9.2995

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Steinberg D (2005) Thematic review series: the pathogenesis of atherosclerosis: an interpretive history of the cholesterol controversy, part III: mechanistically defining the role of hyperlipidemia. J Lipid Res 46(10):2037–2051. https://doi.org/10.1194/jlr.R500010-JLR200

    Article  CAS  PubMed  Google Scholar 

  18. Parthasarathy S, Quinn MT, Steinberg D (1988) Is oxidized low density lipoprotein involved in the recruitment and retention of monocyte/macrophages in the artery wall during the initiation of atherosclerosis? Basic Life Sci 49:375–380. https://doi.org/10.1007/978-1-4684-5568-7_58

    Article  CAS  PubMed  Google Scholar 

  19. Goldstein JL, Ho YK, Basu SK, Brown MS (1979) Binding site on macrophages that mediates uptake and degradation of acetylated low density lipoprotein, producing massive cholesterol deposition. Proc Natl Acad Sci U S A 76(1):333–337. https://doi.org/10.1073/pnas.76.1.333

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Brown MS, Basu SK, Falck JR, Ho YK, Goldstein JL (1980) The scavenger cell pathway for lipoprotein degradation: specificity of the binding site that mediates the uptake of negatively-charged LDL by macrophages. J Supramol Struct 13(1):67–81. https://doi.org/10.1002/jss.400130107

    Article  CAS  PubMed  Google Scholar 

  21. Fogelman AM, Shechter I, Seager J, Hokom M, Child JS, Edwards PA (1980) Malondialdehyde alteration of low density lipoproteins leads to cholesteryl ester accumulation in human monocyte-macrophages. Proc Natl Acad Sci U S A 77(4):2214–2218. https://doi.org/10.1073/pnas.77.4.2214

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Funk CD, Cyrus T (2001) 12/15-lipoxygenase, oxidative modification of LDL and atherogenesis. Trends Cardiovasc Med 11(3–4):116–124. https://doi.org/10.1016/s1050-1738(01)00096-2

    Article  CAS  PubMed  Google Scholar 

  23. Griendling KK, Sorescu D, Ushio-Fukai M (2000) NAD(P)H oxidase: role in cardiovascular biology and disease. Circ Res 86(5):494–501. https://doi.org/10.1161/01.res.86.5.494

    Article  CAS  PubMed  Google Scholar 

  24. Lu T, Parthasarathy S, Hao H, Luo M, Ahmed S, Zhu J, Luo S, Kuppusamy P, Sen CK, Verfaillie CM, Tian J, Liu Z (2010) Reactive oxygen species mediate oxidized low-density lipoprotein-induced inhibition of oct-4 expression and endothelial differentiation of bone marrow stem cells. Antioxid Redox Signal 13(12):1845–1856. https://doi.org/10.1089/ars.2010.3156

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Santanam N, Parthasarathy S (1995) Paradoxical actions of antioxidants in the oxidation of low density lipoprotein by peroxidases. J Clin Invest 95(6):2594–2600. https://doi.org/10.1172/jci117961

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Delporte C, Boudjeltia KZ, Noyon C, Furtmüller PG, Nuyens V, Slomianny MC, Madhoun P, Desmet JM, Raynal P, Dufour D, Koyani CN, Reyé F, Rousseau A, Vanhaeverbeek M, Ducobu J, Michalski JC, Nève J, Vanhamme L, Obinger C, Malle E, Van Antwerpen P (2014) Impact of myeloperoxidase-LDL interactions on enzyme activity and subsequent posttranslational oxidative modifications of apoB-100. J Lipid Res 55(4):747–757. https://doi.org/10.1194/jlr.M047449

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Deevska GM, Sunkara M, Morris AJ, Nikolova-Karakashian MN (2012) Characterization of secretory sphingomyelinase activity, lipoprotein sphingolipid content and LDL aggregation in ldlr−/− mice fed on a high-fat diet. Biosci Rep 32(5):479–490. https://doi.org/10.1042/bsr20120036

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Polacek D, Byrne RE, Scanu AM (1988) Modification of low density lipoproteins by polymorphonuclear cell elastase leads to enhanced uptake by human monocyte-derived macrophages via the low density lipoprotein receptor pathway. J Lipid Res 29(6):797–808

    Article  CAS  PubMed  Google Scholar 

  29. Summerhill VI, Grechko AV, Yet SF, Sobenin IA, Orekhov AN (2019) The atherogenic role of circulating modified lipids in atherosclerosis. Int J Mol Sci 20(14):3561. https://doi.org/10.3390/ijms20143561

    Article  CAS  PubMed Central  Google Scholar 

  30. Orekhov AN, Ivanova EA, Melnichenko AA, Sobenin IA (2017) Circulating desialylated low density lipoprotein. Cor Vasa 59(2):e149–e156. https://doi.org/10.1016/j.crvasa.2016.10.003

    Article  Google Scholar 

  31. Puig N, Montolio L, Camps-Renom P, Navarra L, Jiménez-Altayó F, Jiménez-Xarrié E, Sánchez-Quesada JL, Benitez S (2020) Electronegative LDL promotes inflammation and triglyceride accumulation in macrophages. Cell 9(3):583. https://doi.org/10.3390/cells9030583

    Article  CAS  Google Scholar 

  32. Ivanova EA, Bobryshev YV, Orekhov AN (2015) LDL electronegativity index: a potential novel index for predicting cardiovascular disease. Vasc Health Risk Manag 11:525–532. https://doi.org/10.2147/vhrm.S74697

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Wagner P, Heinecke JW (1997) Copper ions promote peroxidation of low density lipoprotein lipid by binding to histidine residues of apolipoprotein B100, but they are reduced at other sites on LDL. Arterioscler Thromb Vasc Biol 17(11):3338–3346. https://doi.org/10.1161/01.ATV.17.11.3338

    Article  CAS  PubMed  Google Scholar 

  34. Parthasarathy S, Raghavamenon A, Garelnabi MO, Santanam N (2010) Oxidized low-density lipoprotein. Methods Mol Biol 610:403–417. https://doi.org/10.1007/978-1-60327-029-8_24

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Fong LG, Parthasarathy S, Witztum JL, Steinberg D (1987) Nonenzymatic oxidative cleavage of peptide bonds in apoprotein B-100. J Lipid Res 28(12):1466–1477

    Article  CAS  PubMed  Google Scholar 

  36. Fruebis J, Parthasarathy S, Steinberg D (1992) Evidence for a concerted reaction between lipid hydroperoxides and polypeptides. Proc Natl Acad Sci U S A 89(22):10588–10592. https://doi.org/10.1073/pnas.89.22.10588

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Van Antwerpen P, Legssyer I, Zouaoui Boudjeltia K, Babar S, Moreau P, Moguilevsky N, Vanhaeverbeek M, Ducobu J, Nève J (2006) Captopril inhibits the oxidative modification of apolipoprotein B-100 caused by myeloperoxydase in a comparative in vitro assay of angiotensin converting enzyme inhibitors. Eur J Pharmacol 537(1):31–36. https://doi.org/10.1016/j.ejphar.2006.03.022

    Article  CAS  PubMed  Google Scholar 

  38. Gieβauf A, van Wickern B, Simat T, Steinhart H, Esterbauer H (1996) Formation of N-formylkynurenine suggests the involvement of apolipoprotein B-100 centered tryptophan radicals in the initiation of LDL lipid peroxidation. FEBS Lett 389(2):136–140. https://doi.org/10.1016/0014-5793(96)00546-7

    Article  Google Scholar 

  39. Parthasarathy S, Quinn MT, Schwenke DC, Carew TE, Steinberg D (1989) Oxidative modification of beta-very low density lipoprotein. Potential role in monocyte recruitment and foam cell formation. Arteriosclerosis 9(3):398–404. https://doi.org/10.1161/01.atv.9.3.398

    Article  CAS  PubMed  Google Scholar 

  40. Bowry VW, Stanley KK, Stocker R (1992) High density lipoprotein is the major carrier of lipid hydroperoxides in human blood plasma from fasting donors. Proc Natl Acad Sci U S A 89(21):10316–10320. https://doi.org/10.1073/pnas.89.21.10316

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Rijke YBd, Hessels EM, Berkel TJv (1992) Recognition sites on rat liver cells for oxidatively modified beta-very low density lipoproteins. Arterioscl Thromb 12(1):41–49. https://doi.org/10.1161/01.ATV.12.1.41

  42. Bradamante S, Barenghi L, Giudici GA, Vergani C (1992) Free radicals promote modifications in plasma high-density lipoprotein: nuclear magnetic resonance analysis. Free Radic Biol Med 12(3):193–203. https://doi.org/10.1016/0891-5849(92)90027-E

    Article  CAS  PubMed  Google Scholar 

  43. Bonnefont-Rousselot D, Khalil A, Delattre J, Jore D, Gardès-Albert M (1997) Oxidation of human high-density lipoproteins by .OH and .OH/O(.-)2 free radicals. Radiat Res 147(6):721–728

    Article  CAS  PubMed  Google Scholar 

  44. Greilberger J, Jürgens G (1998) Oxidation of high-density lipoprotein HDL3 leads to exposure of apo-AI and apo-AII epitopes and to formation of aldehyde protein adducts, and influences binding of oxidized low-density lipoprotein to type I and type III collagen in vitro1. Biochem J 331(Pt 1):185–191. https://doi.org/10.1042/bj3310185

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Bergt C, Oram JF, Heinecke JW (2003) Oxidized HDL. Arterioscler Thromb Vasc Biol 23(9):1488–1490. https://doi.org/10.1161/01.ATV.0000090570.99836.9C

    Article  CAS  PubMed  Google Scholar 

  46. Asztalos BF (2004) High-density lipoprotein metabolism and progression of atherosclerosis: new insights from the HDL atherosclerosis treatment study. Curr Opin Cardiol 19(4):385–391. https://doi.org/10.1097/01.hco.0000126979.41946.7e

    Article  PubMed  Google Scholar 

  47. Navab M, Ananthramaiah GM, Reddy ST, Van Lenten BJ, Ansell BJ, Fonarow GC, Vahabzadeh K, Hama S, Hough G, Kamranpour N, Berliner JA, Lusis AJ, Fogelman AM (2004) The oxidation hypothesis of atherogenesis: the role of oxidized phospholipids and HDL. J Lipid Res 45(6):993–1007. https://doi.org/10.1194/jlr.R400001-JLR200

    Article  CAS  PubMed  Google Scholar 

  48. Stojanović N, Krilov D, Herak JN (2006) Slow oxidation of high density lipoproteins as studied by EPR spectroscopy. Free Radic Res 40(2):135–140. https://doi.org/10.1080/10715760500456789

    Article  CAS  PubMed  Google Scholar 

  49. Malle E, Marsche G, Panzenboeck U, Sattler W (2006) Myeloperoxidase-mediated oxidation of high-density lipoproteins: fingerprints of newly recognized potential proatherogenic lipoproteins. Arch Biochem Biophys 445(2):245–255. https://doi.org/10.1016/j.abb.2005.08.008

    Article  CAS  PubMed  Google Scholar 

  50. Ferretti G, Bacchetti T, Nègre-Salvayre A, Salvayre R, Dousset N, Curatola G (2006) Structural modifications of HDL and functional consequences. Atherosclerosis 184(1):1–7. https://doi.org/10.1016/j.atherosclerosis.2005.08.008

    Article  CAS  PubMed  Google Scholar 

  51. Kervinen K, Hörkkö S, Beltz WF, Antero Kesaniemi Y (1995) Modification of VLDL apoprotein B by acetaldehyde alters apoprotein B metabolism. Alcohol 12(3):189–194. https://doi.org/10.1016/0741-8329(94)00081-N

    Article  CAS  PubMed  Google Scholar 

  52. Nagano Y, Arai H, Kita T (1991) High density lipoprotein loses its effect to stimulate efflux of cholesterol from foam cells after oxidative modification. Proc Natl Acad Sci U S A 88(15):6457–6461. https://doi.org/10.1073/pnas.88.15.6457

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Ghiselli G, Giorgini L, Gelati M, Musanti R (1992) Oxidatively modified HDLs are potent inhibitors of cholesterol biosynthesis in human skin fibroblasts. Arterioscler Thromb 12(8):929–935. https://doi.org/10.1161/01.ATV.12.8.929

    Article  CAS  PubMed  Google Scholar 

  54. Van Lenten BJ, Wagner AC, Nayak DP, Hama S, Navab M, Fogelman AM (2001) High-density lipoprotein loses its anti-inflammatory properties during acute influenza a infection. Circulation 103(18):2283–2288. https://doi.org/10.1161/01.cir.103.18.2283

    Article  PubMed  Google Scholar 

  55. Jaouad L, Milochevitch C, Khalil A (2003) PON1 paraoxonase activity is reduced during HDL oxidation and is an indicator of HDL antioxidant capacity. Free Radic Res 37(1):77–83. https://doi.org/10.1080/1071576021000036614

    Article  CAS  PubMed  Google Scholar 

  56. Shen J, Herderick E, Cornhill JF, Zsigmond E, Kim HS, Kühn H, Guevara NV, Chan L (1996) Macrophage-mediated 15-lipoxygenase expression protects against atherosclerosis development. J Clin Invest 98(10):2201–2208. https://doi.org/10.1172/jci119029

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Harats D, Shaish A, George J, Mulkins M, Kurihara H, Levkovitz H, Sigal E (2000) Overexpression of 15-lipoxygenase in vascular endothelium accelerates early atherosclerosis in LDL receptor-deficient mice. Arterioscler Thromb Vasc Biol 20(9):2100–2105. https://doi.org/10.1161/01.ATV.20.9.2100

    Article  CAS  PubMed  Google Scholar 

  58. Tribble DL, Gong EL, Leeuwenburgh C, Heinecke JW, Carlson EL, Verstuyft JG, Epstein CJ (1997) Fatty streak formation in fat-fed mice expressing human copper-zinc superoxide dismutase. Arterioscl Thromb Vasc Biol 17(9):1734–1740. https://doi.org/10.1161/01.ATV.17.9.1734

    Article  CAS  PubMed  Google Scholar 

  59. Patel RP, Diczfalusy U, Dzeletovic S, Wilson MT, Darley-Usmar VM (1996) Formation of oxysterols during oxidation of low density lipoprotein by peroxynitrite, myoglobin, and copper. J Lipid Res 37(11):2361–2371

    Article  CAS  PubMed  Google Scholar 

  60. Lamb DJ, Leake DS (1994) Iron released from transferrin at acidic pH can catalyse the oxidation of low density lipoprotein. FEBS Lett 352(1):15–18. https://doi.org/10.1016/0014-5793(94)00903-1

    Article  CAS  PubMed  Google Scholar 

  61. Lamb DJ, Hider RC, Leake DS (1993) Hydroxypyridinones and desferrioxamine inhibit macrophage-mediated LDL oxidation by iron but not by copper. Biochem Soc Trans 21(3):234S–234S. https://doi.org/10.1042/bst021234s

    Article  CAS  PubMed  Google Scholar 

  62. Brennan ML, Anderson MM, Shih DM, Qu XD, Wang X, Mehta AC, Lim LL, Shi W, Hazen SL, Jacob JS, Crowley JR, Heinecke JW, Lusis AJ (2001) Increased atherosclerosis in myeloperoxidase-deficient mice. J Clin Invest 107(4):419–430. https://doi.org/10.1172/jci8797

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. McMillen TS, Heinecke JW, LeBoeuf RC (2005) Expression of human myeloperoxidase by macrophages promotes atherosclerosis in mice. Circulation 111(21):2798–2804. https://doi.org/10.1161/CIRCULATIONAHA.104.516278

    Article  CAS  PubMed  Google Scholar 

  64. Gieseg S, Duggan S, Gebicki JM (2000) Peroxidation of proteins before lipids in U937 cells exposed to peroxyl radicals. Biochem J 350(Pt 1):215–218

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Parthasarathy S (1987) Oxidation of low-density lipoprotein by thiol compounds leads to its recognition by the acetyl LDL receptor. Biochim Biophys Acta 917(2):337–340. https://doi.org/10.1016/0005-2760(87)90139-1

    Article  CAS  PubMed  Google Scholar 

  66. Sparrow CP, Olszewski J (1993) Cellular oxidation of low density lipoprotein is caused by thiol production in media containing transition metal ions. J Lipid Res 34(7):1219–1228

    Article  CAS  PubMed  Google Scholar 

  67. Frei B, Forte TM, Ames BN, Cross CE (1991) Gas phase oxidants of cigarette smoke induce lipid peroxidation and changes in lipoprotein properties in human blood plasma. Protective effects of ascorbic acid. Biochem J 277(Pt 1):133–138. https://doi.org/10.1042/bj2770133

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Bhatnagar A (2004) Cardiovascular pathophysiology of environmental pollutants. Am J Physiol-Heart Circ Physiol 286(2):H479–H485. https://doi.org/10.1152/ajpheart.00817.2003

    Article  CAS  PubMed  Google Scholar 

  69. Bouloumie A, Marumo T, Lafontan M, Busse R (1999) Leptin induces oxidative stress in human endothelial cells. FASEB J 13(10):1231–1238

    Article  CAS  PubMed  Google Scholar 

  70. Santanam N, Shern-Brewer R, McClatchey R, Castellano PZ, Murphy AA, Voelkel S, Parthasarathy S (1998) Estradiol as an antioxidant: incompatible with its physiological concentrations and function. J Lipid Res 39(11):2111–2118

    Article  CAS  PubMed  Google Scholar 

  71. Yamamoto K, Niki E (1988) Interaction of α-tocopherol with iron: antioxidant and prooxidant effects of α-tocopherol in the oxidation of lipids in aqueous dispersions in the presence of iron. Biochim Biophys Acta 958(1):19–23. https://doi.org/10.1016/0005-2760(88)90241-X

    Article  CAS  PubMed  Google Scholar 

  72. Bowry VW, Ingold KU, Stocker R (1992) Vitamin E in human low-density lipoprotein. When and how this antioxidant becomes a pro-oxidant. Biochem J 288(Pt 2):341–344. https://doi.org/10.1042/bj2880341

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Santanam N, Parthasarathy S (1995) Cellular cysteine generation does not contribute to the initiation of LDL oxidation. J Lipid Res 36(10):2203–2211

    Article  CAS  PubMed  Google Scholar 

  74. Graham A, Hogg N, Kalyanaraman B, O'Leary V, Darley-Usmar V, Moncada S (1993) Peroxynitrite modification of low-density lipoprotein leads to recognition by the macrophage scavenger receptor. FEBS Lett 330(2):181–185. https://doi.org/10.1016/0014-5793(93)80269-Z

    Article  CAS  PubMed  Google Scholar 

  75. Noguchi N, Gotoh N, Niki E (1994) Effects of ebselen and probucol on oxidative modifications of lipid and protein of low density lipoprotein induced by free radicals. Biochim Biophys Acta 1213(2):176–182. https://doi.org/10.1016/0005-2760(94)90024-8

    Article  CAS  PubMed  Google Scholar 

  76. Kim JG, Sabbagh F, Santanam N, Wilcox JN, Medford RM, Parthasarathy S (1997) Generation of a polyclonal antibody against lipid peroxide-modified proteins. Free Radic Biol Med 23(2):251–259. https://doi.org/10.1016/s0891-5849(96)00615-6

    Article  CAS  PubMed  Google Scholar 

  77. Dinis TCP, Santos CL, Almeida LM (2002) The apoprotein is the preferential target for peroxynitrite-induced LDL damage protection by dietary phenolic acids. Free Radic Res 36(5):531–543. https://doi.org/10.1080/10715760290025915

    Article  CAS  PubMed  Google Scholar 

  78. Heinecke JW (1997) Pathways for oxidation of low density lipoprotein by myeloperoxidase: tyrosyl radical, reactive aldehydes, hypochlorous acid and molecular chlorine. Biofactors 6(2):145–155. https://doi.org/10.1002/biof.5520060208

    Article  CAS  PubMed  Google Scholar 

  79. Cornicelli JA, Trivedi BK (1999) 15-lipoxygenase and its inhibition: a novel therapeutic target for vascular disease. Curr Pharm Des 5(1):11–20

    CAS  PubMed  Google Scholar 

  80. Kühn H, Römisch I, Belkner J (2005) The role of lipoxygenase-isoforms in atherogenesis. Mol Nutr Food Res 49(11):1014–1029. https://doi.org/10.1002/mnfr.200500131

    Article  CAS  PubMed  Google Scholar 

  81. Benz DJ, Mol M, Ezaki M, Mori-Ito N, Zelán I, Miyanohara A, Friedmann T, Parthasarathy S, Steinberg D, Witztum JL (1995) 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. https://doi.org/10.1074/jbc.270.10.5191

    Article  CAS  PubMed  Google Scholar 

  82. Qian SY, Yue GH, Tomer KB, Mason RP (2003) Identification of all classes of spin-trapped carbon-centered radicals in soybean lipoxygenase-dependent lipid peroxidations of omega-6 polyunsaturated fatty acids via LC/ESR, LC/MS, and tandem MS. Free Radic Biol Med 34(8):1017–1028. https://doi.org/10.1016/s0891-5849(03)00031-5

    Article  CAS  PubMed  Google Scholar 

  83. Palinski W, Rosenfeld ME, Ylä-Herttuala S, Gurtner GC, Socher SS, Butler SW, Parthasarathy S, Carew TE, Steinberg D, Witztum JL (1989) Low density lipoprotein undergoes oxidative modification in vivo. Proc Natl Acad Sci U S A 86(4):1372–1376. https://doi.org/10.1073/pnas.86.4.1372

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Aviram M (1990) Malondialdehyde affects the physico-chemical and biological characteristics of oxidized low density lipoprotein. Atherosclerosis 84(2):141–143. https://doi.org/10.1016/0021-9150(90)90084-V

    Article  CAS  PubMed  Google Scholar 

  85. Lecomte E, Artur Y, Chancerelle Y, Herbeth B, Galteau MM, Jeandel C, Siest G (1993) Malondialdehyde adducts to, and fragmentation of, apolipoprotein B from human plasma. Clin Chim Acta 218(1):39–46. https://doi.org/10.1016/0009-8981(93)90220-x

    Article  CAS  PubMed  Google Scholar 

  86. Requena JR, Fu MX, Ahmed MU, Jenkins AJ, Lyons TJ, Baynes JW, Thorpe SR (1997) Quantification of malondialdehyde and 4-hydroxynonenal adducts to lysine residues in native and oxidized human low-density lipoprotein. Biochem J 322(Pt 1):317–325. https://doi.org/10.1042/bj3220317

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Lyons TJ, Li W, Wells-Knecht MC, Jokl R (1994) Toxicity of mildly modified low-density lipoproteins to cultured retinal capillary endothelial cells and pericytes. Diabetes 43(9):1090–1095. https://doi.org/10.2337/diab.43.9.1090

    Article  CAS  PubMed  Google Scholar 

  88. Scaccini C, Jialal I (1994) LDL modification by activated polymorphonuclear leukocytes: a cellular model of mild oxidative stress. Free Radic Biol Med 16(1):49–55. https://doi.org/10.1016/0891-5849(94)90242-9

    Article  CAS  PubMed  Google Scholar 

  89. Sigari F, Lee C, Witztum JL, Reaven PD (1997) Fibroblasts that overexpress 15-lipoxygenase generate bioactive and minimally modified LDL. Arterioscler Thromb Vasc Biol 17(12):3639–3645. https://doi.org/10.1161/01.ATV.17.12.3639

    Article  CAS  PubMed  Google Scholar 

  90. Kennedy S, Fournet-Bourguignon MP, Breugnot C, Castedo-Delrieu M, Lesage L, Reure H, Briant C, Leonce S, Vilaine JP, Vanhoutte PM (2003) Cells derived from regenerated endothelium of the porcine coronary artery contain more oxidized forms of apolipoprotein-B-100 without a modification in the uptake of oxidized LDL. J Vasc Res 40(4):389–398. https://doi.org/10.1159/000072817

    Article  CAS  PubMed  Google Scholar 

  91. Salonen JT, Ylä-Herttuala S, Yamamoto R, Butler S, Korpela H, Salonen R, Nyyssönen K, Palinski W, Witztum JL (1992) Autoantibody against oxidised LDL and progression of carotid atherosclerosis. Lancet (London, England) 339(8798):883–887. https://doi.org/10.1016/0140-6736(92)90926-t

    Article  CAS  Google Scholar 

  92. Palinski W, Hörkkö S, Miller E, Steinbrecher UP, Powell HC, Curtiss LK, Witztum JL (1996) Cloning of monoclonal autoantibodies to epitopes of oxidized lipoproteins from apolipoprotein E-deficient mice. demonstration of epitopes of oxidized low density lipoprotein in human plasma. J Clin Invest 98(3):800–814. https://doi.org/10.1172/jci118853

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Barros MRAC, Bertolami MC, Abdalla DSP, Ferreira WP (2006) Identification of mildly oxidized low-density lipoprotein (electronegative LDL) and its auto-antibodies IgG in children and adolescents hypercholesterolemic offsprings. Atherosclerosis 184(1):103–107. https://doi.org/10.1016/j.atherosclerosis.2004.11.027

    Article  CAS  PubMed  Google Scholar 

  94. Salmon S, Maziere C, Theron L, Beucler I, Ayrault-Jarrier M, Goldstein S, Polonovski J (1987) Immunological detection of low-density lipoproteins modified by malondialdehyde in vitro or in vivo. Biochim Biophys Acta 920(3):215–220. https://doi.org/10.1016/0005-2760(87)90097-X

    Article  CAS  PubMed  Google Scholar 

  95. Parums DV, Brown DL, Mitchinson MJ (1990) Serum antibodies to oxidized low-density lipoprotein and ceroid in chronic periaortitis. Arch Pathol Lab Med 114(4):383–387

    CAS  PubMed  Google Scholar 

  96. Virella G, Virella I, Leman RB, Pryor MB, Lopes-Virella MF (1993) Anti-oxidized low-density lipoprotein antibodies in patients with coronary heart disease and normal healthy volunteers. Int J Clin Lab Res 23(1):95–101. https://doi.org/10.1007/BF02592290

    Article  CAS  PubMed  Google Scholar 

  97. Holvoet P, Perez G, Zhao Z, Brouwers E, Bernar H, Collen D (1995) Malondialdehyde-modified low density lipoproteins in patients with atherosclerotic disease. J Clin Invest 95(6):2611–2619. https://doi.org/10.1172/jci117963

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. Festa A, Kopp HP, Schernthaner G, Menzel EJ (1998) Autoantibodies to oxidised low density lipoproteins in IDDM are inversely related to metabolic control and microvascular complications. Diabetologia 41(3):350–356. https://doi.org/10.1007/s001250050914

    Article  CAS  PubMed  Google Scholar 

  99. Lehtimäki T, Lehtinen S, Solakivi T, Nikkilä M, Jaakkola O, Jokela H, Ylä-Herttuala S, Luoma JS, Koivula T, Nikkari T (1999) Autoantibodies against oxidized low density lipoprotein in patients with angiographically verified coronary artery disease. Arterioscler Thromb Vasc Biol 19(1):23–27. https://doi.org/10.1161/01.ATV.19.1.23

    Article  PubMed  Google Scholar 

  100. Frostegård J, Wu R, Lemne C, Thulin T, Witztum JL, de Faire U (2003) Circulating oxidized low-density lipoprotein is increased in hypertension. Clin Sci (Lond) 105(5):615–620. https://doi.org/10.1042/cs20030152

    Article  Google Scholar 

  101. Herrick AL, Illingworth KJ, Hollis S, Gomez-Zumaquero JM, Tinahones FJ (2001) Antibodies against oxidized low-density lipoproteins in systemic sclerosis. Rheumatology 40(4):401–405. https://doi.org/10.1093/rheumatology/40.4.401

    Article  CAS  PubMed  Google Scholar 

  102. Tanaga K, Bujo H, Inoue M, Mikami K, Kotani K, Takahashi K, Kanno T, Saito Y (2002) Increased circulating malondialdehyde-modified LDL levels in patients with coronary artery diseases and their association with peak sizes of LDL particles. Arterioscler Thromb Vasc Biol 22(4):662–666. https://doi.org/10.1161/01.atv.0000012351.63938.84

    Article  CAS  PubMed  Google Scholar 

  103. Meraviglia MV, Maggi E, Bellomo G, Cursi M, Fanelli G, Minicucci F (2002) Autoantibodies against oxidatively modified lipoproteins and progression of carotid restenosis after carotid endarterectomy. Stroke 33(4):1139–1141. https://doi.org/10.1161/01.STR.0000014420.15948.2E

    Article  CAS  PubMed  Google Scholar 

  104. Hsu RM, Devaraj S, Jialal I (2002) Autoantibodies to oxidized low-density lipoprotein in patients with type 2 diabetes mellitus. Clin Chim Acta 317(1):145–150. https://doi.org/10.1016/S0009-8981(01)00767-7

    Article  CAS  PubMed  Google Scholar 

  105. Tsimikas S, Bergmark C, Beyer RW, Patel R, Pattison J, Miller E, Juliano J, Witztum JL (2003) Temporal increases in plasma markers of oxidized low-density lipoprotein strongly reflect the presence of acute coronary syndromes. J Am Coll Cardiol 41(3):360–370. https://doi.org/10.1016/s0735-1097(02)02769-9

    Article  CAS  PubMed  Google Scholar 

  106. Wang J, Qiang H, Zhang C, Liu X, Chen D, Wang S (2003) Detection of IgG-bound lipoprotein(a) immune complexes in patients with coronary heart disease. Clin Chim Acta 327(1):115–122. https://doi.org/10.1016/S0009-8981(02)00342-X

    Article  CAS  PubMed  Google Scholar 

  107. Koskenmies S, Vaarala O, Widen E, Kere J, Palosuo T, Julkunen H (2004) The association of antibodies to cardiolipin, beta 2-glycoprotein I, prothrombin, and oxidized low-density lipoprotein with thrombosis in 292 patients with familial and sporadic systemic lupus erythematosus. Scand J Rheumatol 33(4):246–252. https://doi.org/10.1080/03009740410005386

    Article  CAS  PubMed  Google Scholar 

  108. Luoma JS, Kareinen A, Närvänen O, Viitanen L, Laakso M, Ylä-Herttuala S (2005) Autoantibodies against oxidized LDL are associated with severe chest pain attacks in patients with coronary heart disease. Free Radic Biol Med 39(12):1660–1665. https://doi.org/10.1016/j.freeradbiomed.2005.08.007

    Article  CAS  PubMed  Google Scholar 

  109. Yamaguchi Y, Yoshikawa N, Kagota S, Nakamura K, Haginaka J, Kunitomo M (2006) Elevated circulating levels of markers of oxidative-nitrative stress and inflammation in a genetic rat model of metabolic syndrome. Nitric Oxide 15(4):380–386. https://doi.org/10.1016/j.niox.2006.04.264

    Article  CAS  PubMed  Google Scholar 

  110. Kim JG, Taylor WR, Parthasarathy S (1999) Demonstration of the presence of lipid peroxide-modified proteins in human atherosclerotic lesions using a novel lipid peroxide-modified anti-peptide antibody. Atherosclerosis 143(2):335–340. https://doi.org/10.1016/S0021-9150(98)00320-7

    Article  CAS  PubMed  Google Scholar 

  111. Wall SB, Oh JY, Diers AR, Landar A (2012) Oxidative modification of proteins: an emerging mechanism of cell signaling. Front Physiol 3:369. https://doi.org/10.3389/fphys.2012.00369

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  112. Esterbauer H, Striegl G, Puhl H, Rotheneder M (1989) Continuous monitoring of in vitro oxidation of human low density lipoprotein. Free Radic Res Commun 6(1):67–75. https://doi.org/10.3109/10715768909073429

    Article  CAS  PubMed  Google Scholar 

  113. Moore K, Roberts LJ 2nd (1998) Measurement of lipid peroxidation. Free Radic Res 28(6):659–671. https://doi.org/10.3109/10715769809065821

    Article  CAS  PubMed  Google Scholar 

  114. Moore KP, Darley-Usmar V, Morrow J, Roberts LJ (1995) Formation of F2-isoprostanes during oxidation of human low-density lipoprotein and plasma by peroxynitrite. Circ Res 77(2):335–341. https://doi.org/10.1161/01.RES.77.2.335

    Article  CAS  PubMed  Google Scholar 

  115. Gugliucci Creriche A, Stahl AJ (1993) Glycation and oxidation of human low density lipoproteins reduces heparin binding and modifies charge. Scand J Clin Lab Invest 53(2):125–132. https://doi.org/10.3109/00365519309088399

    Article  CAS  PubMed  Google Scholar 

  116. Sánchez-Quesada JL, Pérez A, Caixàs A, Ordónmez-Llanos J, Carreras G, Payés A, González-Sastre F, de Leiva A (1996) Electronegative low density lipoprotein subform is increased in patients with short-duration IDDM and is closely related to glycaemic control. Diabetologia 39(12):1469–1476. https://doi.org/10.1007/s001250050600

    Article  PubMed  Google Scholar 

  117. Demuth K, Myara I, Chappey B, Vedie B, Pech-Amsellem MA, Haberland ME, Moatti N (1996) A cytotoxic electronegative LDL subfraction is present in human plasma. Arterioscler Thromb Vasc Biol 16(6):773–783. https://doi.org/10.1161/01.atv.16.6.773

    Article  CAS  PubMed  Google Scholar 

  118. Dai L, Zhang Z, Winyard PG, Gaffney K, Jones H, Blake DR, Morris CJ (1997) A modified form of low-density lipoprotein with increased electronegative charge is present in rheumatoid arthritis synovial fluid. Free Radic Biol Med 22(4):705–710. https://doi.org/10.1016/s0891-5849(96)00389-9

    Article  CAS  PubMed  Google Scholar 

  119. Moro E, Zambon C, Pianetti S, Cazzolato G, Pais M, Bittolo Bon G (1998) 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. https://doi.org/10.1007/s005920050123

    Article  CAS  PubMed  Google Scholar 

  120. Sánchez-Quesada JL, Camacho M, Antón R, Benítez S, Vila L, Ordóñez-Llanos J (2003) Electronegative LDL of FH subjects: chemical characterization and induction of chemokine release from human endothelial cells. Atherosclerosis 166(2):261–270. https://doi.org/10.1016/s0021-9150(02)00374-x

    Article  PubMed  Google Scholar 

  121. Parasassi T, Bittolo-Bon G, Brunelli R, Cazzolato G, Krasnowska EK, Mei G, Sevanian A, Ursini F (2001) Loss of apoB-100 secondary structure and conformation in hydroperoxide rich, electronegative LDL(−). Free Radic Biol Med 31(1):82–89. https://doi.org/10.1016/s0891-5849(01)00555-x

    Article  CAS  PubMed  Google Scholar 

  122. Aluganti Narasimhulu C, Selvarajan K, Brown M, Parthasarathy S (2014) Cationic peptides neutralize ox-LDL, prevent its uptake by macrophages, and attenuate inflammatory response. Atherosclerosis 236(1):133–141. https://doi.org/10.1016/j.atherosclerosis.2014.06.020

    Article  CAS  PubMed  Google Scholar 

  123. Chandrakala AN, Sukul D, Selvarajan K, Sai-Sudhakar C, Sun B, Parthasarathy S (2012) Induction of brain natriuretic peptide and monocyte chemotactic protein-1 gene expression by oxidized low-density lipoprotein: relevance to ischemic heart failure. Am J Physiol Cell Physiol 302(1):C165–C177. https://doi.org/10.1152/ajpcell.00116.2011

    Article  CAS  PubMed  Google Scholar 

  124. Selvarajan K, Narasimhulu CA, Bapputty R, Parthasarathy S (2015) Anti-inflammatory and antioxidant activities of the nonlipid (aqueous) components of sesame oil: potential use in atherosclerosis. J Med Food 18(4):393–402. https://doi.org/10.1089/jmf.2014.0139

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  125. Selvarajan K, Moldovan L, Chandrakala AN, Litvinov D, Parthasarathy S (2011) Peritoneal macrophages are distinct from monocytes and adherent macrophages. Atherosclerosis 219(2):475–483. https://doi.org/10.1016/j.atherosclerosis.2011.09.014

    Article  CAS  PubMed  Google Scholar 

  126. Aluganti Narasimhulu C, Burge KY, Doomra M, Riad A, Parthasarathy S (2018) Primary prevention of atherosclerosis by pretreatment of low-density lipoprotein receptor knockout mice with sesame oil and its aqueous components. Sci Rep 8(1):12270. https://doi.org/10.1038/s41598-018-29849-x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  127. Deme P, Aluganti Narasimhulu C, Parthasarathy S (2019) Evaluation of anti-inflammatory properties of herbal aqueous extracts and their chemical characterization. J Med Food 22(8):861–873. https://doi.org/10.1089/jmf.2019.0009

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  128. Barrett R, Narasimhulu CA, Parthasarathy S (2018) Adrenergic hormones induce extrapituitary prolactin gene expression in leukocytes-potential implications in obesity. Sci Rep 8(1):1936. https://doi.org/10.1038/s41598-018-20378-1

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  129. Sengupta B, Narasimhulu CA, Parthasarathy S (2013) Novel technique for generating macrophage foam cells for in vitro reverse cholesterol transport studies. J Lipid Res 54(12):3358–3372. https://doi.org/10.1194/jlr.M041327

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  130. Fernandez-Ruiz I, Puchalska P, Narasimhulu CA, Sengupta B, Parthasarathy S (2016) Differential lipid metabolism in monocytes and macrophages: influence of cholesterol loading. J Lipid Res 57(4):574–586. https://doi.org/10.1194/jlr.M062752

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  131. Narasimhulu CA, Vardhan S (2015) Therapeutic potential of ocimum tenuiflorum as MPO inhibitor with implications for atherosclerosis prevention. J Med Food 18(5):507–515. https://doi.org/10.1089/jmf.2014.0125

    Article  CAS  PubMed  Google Scholar 

  132. Tien M (1999) Myeloperoxidase-catalyzed oxidation of tyrosine. Arch Biochem Biophys 367(1):61–66. https://doi.org/10.1006/abbi.1999.1226

    Article  CAS  PubMed  Google Scholar 

  133. Vlasova II, Sokolov AV, Arnhold J (2012) The free amino acid tyrosine enhances the chlorinating activity of human myeloperoxidase. J Inorg Biochem 106(1):76–83. https://doi.org/10.1016/j.jinorgbio.2011.09.018

    Article  CAS  PubMed  Google Scholar 

  134. Aluganti Narasimhulu C, Litvinov D, Sengupta B, Jones D, Sai-Sudhakar C, Firstenberg M, Sun B, Parthasarathy S (2016) Increased presence of oxidized low-density lipoprotein in the left ventricular blood of subjects with cardiovascular disease. Physiol Rep 4(6):e12726. https://doi.org/10.14814/phy2.12726

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Chandrakala Aluganti Narasimhulu .

Editor information

Editors and Affiliations

Additional information

Sampath Parthasarathy is deceased at the time of publication. This chapter is dedicated to his memory.

Rights and permissions

Reprints and permissions

Copyright information

© 2022 The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature

About this protocol

Check for updates. Verify currency and authenticity via CrossMark

Cite this protocol

Aluganti Narasimhulu, C., Parthasarathy, S. (2022). Preparation of LDL , Oxidation , Methods of Detection, and Applications in Atherosclerosis Research. In: Ramji, D. (eds) Atherosclerosis. Methods in Molecular Biology, vol 2419. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-1924-7_13

Download citation

  • DOI: https://doi.org/10.1007/978-1-0716-1924-7_13

  • Published:

  • Publisher Name: Humana, New York, NY

  • Print ISBN: 978-1-0716-1923-0

  • Online ISBN: 978-1-0716-1924-7

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics