Abstract
A minor, more electronegatively charged, sub-fraction (LDL-) was isolated from plasma LDL by ion exchange HPLC and characterized as a mildly oxidized LDL. In samples obtained from normal donors HPLC analysis of OPA derivatized amino-acids, reverse phase HPLC of phospho-lipids and GC analysis of oxysterols was performed in both normally charged LDL (nLDL) and LDL-. In LDL- a significant decrease of aspartic acid, histidine, threonine, isoleucine, leucine and lysine was found, whereas serine, glycine and alanine increased. Among phospholipid classes there was a decrease in phosphatidylcholine and an increase in lysophosphatidylcholine in LDL- as compared to nLDL; also the percentage content of phosphoinositol, phosphatidtlserine and phosphatidylhetanolamine was increased in LDL-. Furthermore, a specific increase in cholestan-3,5-diene-7-one and 7-β-hydroxycholesterol, along with an increase in total oxysterols were found in LDL-. Some of the observed characteristics (reduction of histidine and lysine residues, increase of lyso-phosphatidylcholine and presence of oxysterols) have been previously reported in LDL oxidized by metal ions or by endothelial cells cultures. These data support the hypothesis that the LDL- subtraction may originate from native LDL, through a mild oxidative process occurring “in vivo”.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Steinberg D., Parthasarathy S., Carew, T.E., Khoo, J.C., and Witztum, J.L. (1989) ‘Beyond cholesterol: modifications of low density lipoprotein that increase its atherogenicity’, N. Engl. J. Med. 320, 915–924.
Henriksen T., Mahoney, E.M., and Steinberg, D. (1981) ‘Enhanced macrophage degradation of low density lipoprotein previously incubated with cultured endothelial cells: recognition by receptors for acetylated low density lipoproteins’, Proc. Natl. Acad. Sci. USA 78, 6499–6503.
Heinecke, J.W., Baker L., Rosen H., and Chait, A. (1986) ‘Superoxide-mediated modification of low density lipoprotein by arterial smooth muscle cells’, J. Clin. Invest. 77, 757–763.
Parthasarathy S., Printz, D.J., Boyd D., Joy L., and Steinberg, D. (1986) ‘Macrophage oxidation of low density lipoprotein generates — form recognized by the scavenger receptor’, Arteriosclerosis 6, 505–510.
Heinecke, J.W., Rosen H., and Chait, A. (1987) ‘Iron and copper promote modification of low-density lipoprotein by human arterial smooth muscle cells in culture’, J. Clin. Invest. 74, 1890–1984.
Palinsky W., Rosenfeld, M.E., Yla-Herttula S., Gurtner, G.C., Socher, S.S., Butler, S.W., Parthasarathy S., Carew, T.E., Steinberg D., and Witztum, J.L. (1989) ‘Low-density lipoprotein undergoes oxidative modification in vivo’, Proc. Natl. Acad. Sci. USA 86, 1372–1376.
Haberland M., Fong D., and Cheng, L. (1988), ‘Malondialdehyde-altered proteins occurs in atheroma of Watanabe heritable hyperlipidemic rabbits’, Science 241, 215–218.
Yagi, K. (1987) ‘Lipid peroxides and human diseases’ Chem. Phys. Lipids 45, 337–351.
Morel, D.W., and Chisolm, G.M. (1989) ‘Antioxidant treatment of diabetic rats inhibits lipoprotein oxidation and cytotoxicity’, J. Lipid Res. 30, 1827–1834.
Harats D., Ben-Nairn M., Dabach Y., Hollander, G, Havivi E., Stein O., and Stein, Y. (1990) ‘Effect of vitamin — and — supplementation on susceptibility of plasma lipoproteins to peroxidation induced by acute smoking’, Atherosclerosis 85, 47–54.
Witztum, J.L., and Steinberg, D., (1991) ‘Role of oxidized low density lipoproteins in atherogenesis’, J. Clin. Invest. 88, 1185–1192.
Avogaro P., Bittolo-Bon, G, and Cazzolato, G, (1988) Presence of — modified low density lipoprotein in humans’, Arteriosclerosis 8, 79–81.
Cazzolato G., Avogaro P., and Bittolo-Bon, G, (1991) ‘Characterization of — more electronegatively charged LDL subtraction by ion exchange HPLC, Free Radical Biol. Med. 11, 247–253.
Avogaro P., Cazzolato, G, and Bittolo-Bon, G, (1991) ‘Some questions concerning — small, more electronegative LDL circulating in human plasma’, Atherosclerosis 91, 163–171.
Havel R.J., Eder H.A., and Bragdon J.H., (1955) ‘The distribution and chemical composition of ultracentrifugally separated lipoproteins in human serum’, J. Clin. Invest. 34, 1345–1351.
Jones B.N., and Gillifan J.P., (1983) ‘O-Phtalaldialdehyde precolumn derivatization and reversed-phase HPLC of polypeptide hydrolysates and physiological fluids’, J. Chromatography 266, 471–482.
Hodis H.N., Crawford D.W., ans Sevanian A., (1991) ‘Cholesterol feeding increses plasma and aortic tissue cholesterol oxide levels in parallel: further evidence for the role of cholesterol oxidation in atherosclerosis’, Atherosclerosis 89, 117–126.
Kane J.P., Hardman D.A., and Paulus H.P., (1980) ‘Heterogeneneity of apolipoprotein B: isolation of — new species from human chylomicrons’, Proc. Natl. Acad. Sci. USA 77, 2465–2469.
Fong L.G, Parthasarathy S., Witztum J.L., and Steinberg D., (1987) ‘Nonenzymatic oxidative cleavage of peptide bonds in apoprotein B-100’, J. Lipid Res. 28, 1466–1477.
Quinn M.T., Parthasarathy S., Fong L.G, and Steinberg D., (1987) Oxidatively modified low density lipoproteins: — potential role in recruitment and retention of monocyte/macrophages during atherogenesis’, Proc. Natl. Acad. Sci. USA 84, 2995–2998.
Berliner J.A, Territo M.C., Sevanian A., Ramin S., Kim J.A., Esterson M, and Fogelman A.M., (1990) Minimally modified LDL stimulates monocyte endothelial interactions’, J. Clin. Invest. 85, 1260–1266.
Kugiyama K., Kerns S.A, Morrisett J.D., Roberts R., and Henry P.D., (1990) ‘Impairment of endothelium-dependent arterial relaxation by lisolecithin in modified low density lipoproteins’, Nature 344, 160–162.
Parthasarathy S., and Barnett J., (1990) ‘Phospholipase A2 activity of low density lipoprotein: evidence for an intrinsic phospholipase A2 activity of apolipoprotein B-100’, Proc. Natl. Acad. Sci. USA 87, 9741–9745.
Zhang H., Harkamal J.K.B., and Steinbrecher U.P.,(1990) Effect of oxidatively modified LDL on cholesterol esterification in cultured macrophages’, J. Lipid Res. 31, 1361–1369.
Peng S.K., Hu B., and Morin R.J., (1991) ‘Angiotoxicity and atherogenicity of cholesterol oxides’, J. Clin. Lab. Ana. 5, 144–152.
Sevanian A., Berliner J., and Patterson H., (1991) ‘Uptake, metabolism and cytotoxicity of isolmeric cholesterol-5,6-epoxides in rabbit aortic endothelial cells’, — Lipid Res. 32, 147–155.
Chisolm G.M., Kimberly C, and Perm M.S., (1992) ‘Lipoprotein oxidation and lipoprotein-induced cell injury in diabetes’, Diabetes 41 (Suppl. 2), 61–66.
Hodis H.N., Kramsh D.M., Sevanian A, Avogaro P., Bittolo-Bon G., Cazzolato G., Hwang G, and Peterson H.’ Biochemical and cytotoxic characteristics of an in vivo circulating oxidized low density lipoprotein (LDL-)’, in the press.
Van Hinsberg V.H.M., Sheffer M., Haveks L., Kempen H.J.R. (1986) ‘Role of endothelial cells in the modification of low density lipoproteins’, Biochim. Biophys. Acta 878, 49–64.
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1993 Springer Science+Business Media Dordrecht
About this chapter
Cite this chapter
Cazzolato, G., Kramsch, D.M., Sevanian, A., Hodis, H., Bittolo Bon, G., Avogaro, P. (1993). Oxidative Damage to Circulating LDL. In: Catapano, A.L., Gotto, A.M., Smith, L.C., Paoletti, R. (eds) Drugs Affecting Lipid Metabolism. Medical Science Symposia Series, vol 2. Springer, Dordrecht. https://doi.org/10.1007/978-94-011-1703-6_25
Download citation
DOI: https://doi.org/10.1007/978-94-011-1703-6_25
Publisher Name: Springer, Dordrecht
Print ISBN: 978-94-010-4746-3
Online ISBN: 978-94-011-1703-6
eBook Packages: Springer Book Archive