Advertisement
Research Article| Volume 30, ISSUE 3, P248-255, December 2002

Download started.

Ok

Low density lipoprotein oxidized in xanthoma tissue induces the formation and infiltration of foam cells

      Abstract

      Human low density lipoprotein (LDL) was incubated with rabbit xanthoma tissue or non-lesional dermis. The xanthoma tissue-modified LDL (x-LDL) was oxidized showing a 12-fold higher level of thiobarbituric acid-reactive substances (TBARSs) and a faster anodic electrophoretic mobility than native LDL (n-LDL). The LDL treated with non-lesional dermis (d-LDL) had a twofold higher TBARS level compared with n-LDL, but the electrophoretic mobility of d-LDL and n-LDL was similar. Cholesterol esterifying activity in mouse peritoneal macrophages, an indicator of LDL uptake, was up-regulated 5-fold and 1.8-fold by incubation with x-LDL and d-LDL, respectively, compared with n-LDL. Macrophages transformed into foam cells in incubation with x-LDL, and intradermal injections of x-LDL induced infiltration of great many foam cells in the normolipemic rabbit dermis. d-LDL had much less effects on the foam cell formation and foam cell infiltration than x-LDL. Cholesterol:protein ratio was higher in x-LDL than in n-LDL and d-LDL, suggesting that x-LDL-induced foam cells accumulated the lipids by incorporating the cholesterol-rich x-LDL. In conclusion, extravasated LDL receives oxidation and contributes to foam cell recruitment in xanthoma lesions. On the other hand, extravasated LDL in non-lesional dermis receives limited oxidation and additional promoting factors are necessary for initiation of xanthoma development.

      Keywords

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Journal of Dermatological Science
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Parthasarathy S.
        • Steinberg D.
        • Witztum J.L.
        The role of oxidized low density lipoproteins in the pathogenesis of atherosclerosis.
        Annu. Rev. Med. 1992; 43: 219-225
        • Steinberg D.
        • Parthasarathy S.
        • Carew T.E.
        • Khoo J.C.
        • Witztum J.L.
        Beyond cholesterol: modifications of low density lipoprotein that increase its atherogenicity.
        N. Engl. J. Med. 1989; 320: 915-924
        • Steinbrecher U.P.
        • Zhang H.F.
        • Lougheed M.
        Role of oxidatively modified LDL in atherosclerosis.
        Free Radic. Biol. Med. 1990; 9: 155-168
        • Kume N.
        • Cybulsky M.I.
        • Gimbrone M.J.
        Lysophosphatidylcholine, a component of atherogenic lipoproteins, induces mononuclear leukocyte adhesion molecules in cultured human and rabbit arterial endothelial cells.
        J. Clin. Invest. 1992; 90: 1138-1144
        • Kim J.A.
        • Territo M.C.
        • Wayner E.
        • Carlos T.M.
        • Parhami F.
        • Smith C.W.
        • Haberland M.E.
        • Fogelman A.M.
        • Berliner J.A.
        Partial characterization of leukocyte binding molecules on endothelial cells induced by minimally oxidized LDL.
        Arterioscler. Thromb. 1994; 14: 427-433
        • Chisolm G.M.
        Oxidized lipoproteins and leukocyte–endothelial interactions: growing evidence for multiple mechanisms.
        Lab. Invest. 1993; 68: 369-371
        • Steinbrecher U.P.
        Receptors for oxidized low density lipoprotein.
        Biochim. Biophys. Acta. 1999; 1436: 279-298
        • Parthasarathy S.
        • Wieland E.
        • Steinberg D.
        A role for endothelial cell lipoxygenase in the oxidative modification of low density lipoprotein.
        Proc. Natl. Acad. Sci. USA. 1989; 86: 1046-1050
        • Heinecke J.W.
        • Rosen H.
        • Suzuki L.A.
        • Chait A.
        The role of sulfur-containing amino acids in superoxide production and modification of low density lipoprotein by arterial smooth muscle cells.
        J. Biol. Chem. 1987; 262: 10098-10103
        • Cathcart M.K.
        • Chisolm G.M.
        • McNally A.K.
        • Morel D.W.
        Oxidative modification of low density lipoprotein (LDL) by activated human monocytes and the cell lines U937 and HL60.
        In Vitro Cell. Dev. Biol. 1988; 24: 1001-1008
        • Parthasarathy S.
        • Printz D.J.
        • Boyd D.
        • Joy L.
        • Steinberg D.
        Macrophage oxidation of low density lipoprotein generates a modified form recognized by the scavenger receptor.
        Arteriosclerosis. 1986; 6: 505-510
        • Steinbrecher U.P.
        Role of superoxide in endothelial-cell modification of low density lipoproteins.
        Biochim. Biophys. Acta. 1988; 959: 20-30
        • Kodama H.
        • Akiyama H.
        • Nagao Y.
        • Akagi O.
        • Nohara N.
        Persistence of foam cells in rabbit xanthoma after normalization of serum cholesterol level.
        Arch. Dermatol. Res. 1988; 280: 108-113
        • Kodama H.
        • Nagao Y.
        • Arakawa K.
        • Tada J.
        • Nohara N.
        Cholesterol synthesis and esterification in experimental xanthoma tissues.
        J. Lipid Res. 1981; 22: 1033-1041
        • Hatch F.T.
        Practical methods for plasma lipoprotein analysis.
        Adv. Lipid Res. 1968; 6: 1-68
        • Yagi K.
        Simple assay for the level of total lipid peroxides in serum or plasma.
        Meth. Mol. Biol. 1998; 108: 101-106
        • Brown M.S.
        • Goldstein J.L.
        • Krieger M.
        • Ho Y.K.
        • Anderson R.G.
        Reversible accumulation of cholesteryl esters in macrophages incubated with acetylated lipoproteins.
        J. Cell Biol. 1979; 82: 597-613
        • St Clair R.W.
        • Smith B.P.
        • Wood L.L.
        Stimulation of cholesterol esterification in rhesus monkey arterial smooth muscle cells.
        Circ. Res. 1977; 40: 166-173
        • Cathcart M.K.
        • McNally A.K.
        • Morel D.W.
        • Chisolm G.M.
        Superoxide anion participation in human monocyte-mediated oxidation of low density lipoprotein and conversion of low density lipoprotein to a cytotoxin.
        J. Immunol. 1989; 142: 1963-1969
        • Rankin S.M.
        • Parthasarathy S.
        • Steinberg D.
        Evidence for a dominant role of lipoxygenase(s) in the oxidation of LDL by mouse peritoneal macrophages.
        J. Lipid Res. 1991; 32: 449-456
        • Heinecke J.W.
        • Rosen H.
        • Chait A.
        Iron and copper promote modification of low density lipoprotein by human arterial smooth muscle cells in culture.
        J. Clin. Invest. 1984; 74: 1890-1894
        • Leake D.S.
        • Rankin S.M.
        The oxidative modification of low density lipoproteins by macrophages.
        Biochem. J. 1990; 270: 741-748
        • Lamb D.J.
        • Mitchinson M.J.
        • Leake D.S.
        Transition metal ions within human atherosclerotic lesions can catalyse the oxidation of low density lipoprotein by macrophages.
        FEBS Lett. 1995; 374: 12-16
        • Ylä-Herttuala S.
        • Palinski W.
        • Rosenfeld M.E.
        • Parthasarathy S.
        • Carew T.E.
        • Butler S.
        • Witztum J.L.
        • Steinberg D.
        Evidence for the presence of oxidatively modified low density lipoprotein in atherosclerotic lesions of rabbit and man.
        J. Clin. Invest. 1989; 84: 1086-1095
        • Rosenfeld M.E.
        • Palinski W.
        • Ylä-Herttuala S.
        • Butler S.
        • Witztum J.L.
        Distribution of oxidation specific lipid-protein adducts and apolipoprotein B in atherosclerotic lesions of varying severity from WHHL rabbits.
        Arteriosclerosis. 1990; 10: 336-349
        • Palinski W.
        • Rosenfeld M.E.
        • Ylä-Herttuala S.
        • Gurtner G.C.
        • Socher S.S.
        • Butler S.W.
        • Parthasarathy S.
        • Carew T.E.
        • Steinberg D.
        • Witztum J.L.
        Low density lipoprotein undergoes oxidative modification in vivo.
        Proc. Natl. Acad. Sci. USA. 1989; 86: 1372-1376
        • Hoff H.F.
        • O'Neil J.
        Extracts of human atherosclerotic lesions can modify low density lipoproteins leading to enhanced uptake by macrophages.
        Atherosclerosis. 1988; 70: 29-41
        • Morton R.E.
        • West G.A.
        • Hoff H.F.
        A low density lipoprotein-sized particle isolated from human atherosclerotic lesions is internalized by macrophages via a non-scavenger-receptor mechanism.
        J. Lipid Res. 1986; 27: 1124-1134
        • Daugherty A.
        • Zweifel B.S.
        • Sobel B.E.
        • Schonfeld G.
        Isolation of low density lipoprotein from atherosclerotic vascular tissue of Watanabe heritable hyperlipidemic rabbits.
        Arteriosclerosis. 1988; 8: 768-777
        • Quinn M.T.
        • Parthasarathy S.
        • Fong L.G.
        • Steinberg D.
        Oxidatively modified low density lipoproteins: a potential role in recruitment and retention of monocyte/macrophages during atherogenesis.
        Proc. Natl. Acad. Sci. USA. 1987; 84: 2995-2998