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Continued inhibition of atherosclerotic lesion development in long term Western diet fed CD36°/apoE° mice

      Abstract

      We previously determined that absence of CD36 inhibited atherosclerosis lesion development in 12-week Western diet fed apoE° mice, and this was due largely to absence of macrophage CD36. It is possible that at later stages of disease this effect would be lost due to the progressive nature of lesion development and involvement of other factors. However, lesion development continues to be characterized by recruitment of macrophages and foam cell formation, thus it is also possible that delay in lipid accumulation as a result of absence of CD36 would continue to retard lesion development. The objective of this study was to determine if absence of CD36 continued to inhibit lesion formation. Background matched apoE° and CD36°/apoE° mice were fed a Western diet for up to 35 weeks. At 20 and 35 weeks, lesion area was 25 and 35% less, respectively, in CD36°/apoE° mice. Most impressive was the difference in gross appearance of the aortas at 35 weeks: apoE° aortas were sclerotic and nearly occluded by lesion, whereas aortas from CD36°/apoE° mice had smaller lesions that were more punctate. We conclude that absence of CD36 continues to reduce lesion burden even at late stages of disease in the apoE° model.

      Abbreviations:

      apoE° (apolipoprotein E knock out), CD36° (CD36 knock out), HDL (high density lipoprotein), HIV (human immunodeficiency virus), IACUC (institutional animal care and use committee), LDL (low density lipoprotein), LOX-1 (lectin-like low density lipoprotein receptor), MPO (myeloperoxidase), NEFA (non-esterified fatty acids), PBS (phosphate buffered saline), PCR (polymerase chain reaction), PPAR (peroxisome proliferator activated receptor), SRA-I/II (scavenger receptor A I/II)

      Keywords

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      References

        • Febbraio M.
        • Hajjar D.P.
        • Silverstein R.L.
        CD36: a class B scavenger receptor involved in angiogenesis, atherosclerosis, inflammation, and lipid metabolism.
        J Clin Invest. 2001; 108: 785-791
        • Endemann G.
        • Stanton L.W.
        • Madden K.S.
        • Bryant C.M.
        • White R.T.
        • Protter A.A.
        CD36 is a receptor for oxidized low density lipoprotein.
        J Biol Chem. 1993; 268: 11811-11816
        • Podrez E.A.
        • Febbraio M.
        • Sheibani N.
        • et al.
        Macrophage scavenger receptor CD36 is the major receptor for LDL modified by monocyte-generated reactive nitrogen species.
        J Clin Invest. 2000; 105: 1095-1108
        • Podrez E.A.
        • Poliakov E.
        • Shen Z.
        • et al.
        Identification of a novel family of oxidized phospholipids that serve as ligands for the macrophage scavenger receptor CD36.
        J Biol Chem. 2002; 277: 38503-38516
        • Sun M.
        • Finnemann S.C.
        • Febbraio M.
        • et al.
        Light-induced oxidation of photoreceptor outer segment phospholipids generates ligands for CD36-mediated phagocytosis by retinal pigment epithelium: a potential mechanism for modulating outer segment phagocytosis under oxidant stress conditions.
        J Biol Chem. 2006; 281: 4222-4230
        • Podrez E.A.
        • Poliakov E.
        • Shen Z.
        • et al.
        A novel family of atherogenic oxidized phospholipids promotes macrophage foam cell formation via the scavenger receptor CD36 and is enriched in atherosclerotic lesions.
        J Biol Chem. 2002; 277: 38517-38523
        • Ren Y.
        • Silverstein R.L.
        • Allen J.
        • Savill J.
        CD36 gene transfer confers capacity for phagocytosis of cells undergoing apoptosis.
        J Exp Med. 1995; 181: 1857-1862
        • Halpern M.J.
        Lipids and atherosclerosis.
        Mol Aspects Med. 1995; 16: 509-710
        • Aikawa M.
        • Libby P.
        Lipid lowering therapy in atherosclerosis.
        Semin Vasc Med. 2004; 4: 357-366
        • Lusis A.J.
        Atherosclerosis.
        Nature. 2000; 407: 233-241
        • Maor I.
        • Hayek T.
        • Coleman R.
        • Aviram M.
        Plasma LDL oxidation leads to its aggregation in the atherosclerotic apolipoprotein E-deficient mice.
        Arterioscler Thromb Vasc Biol. 1997; 17: 2995-3005
        • van Berkel T.J.
        • Out R.
        • Hoekstra M.
        • Kuiper J.
        • Biessen E.
        • van Eck M.
        Scavenger receptors: friend or foe in atherosclerosis?.
        Curr Opin Lipidol. 2005; 16: 525-535
        • Ross R.
        Atherosclerosis—an inflammatory disease.
        N Engl J Med. 1999; 340: 115-126
        • Zhao Z.
        • de Beer M.C.
        • Cai L.
        • et al.
        Low-density lipoprotein from apolipoprotein E-deficient mice induces macrophage lipid accumulation in a CD36 and scavenger receptor class A-dependent manner.
        Arterioscler Thromb Vasc Biol. 2005; 25: 168-173
        • Febbraio M.
        • Podrez E.A.
        • Smith J.D.
        • et al.
        Targeted disruption of the class B scavenger receptor CD36 protects against atherosclerotic lesion development in mice.
        J Clin Invest. 2000; 105: 1049-1056
        • Febbraio M.
        • Guy E.
        • Silverstein R.L.
        Stem cell transplantation reveals that absence of macrophage CD36 is protective against atherosclerosis.
        Arterioscler Thromb Vasc Biol. 2004; 24: 2333-2338
        • Moore K.J.
        • Kunjathoor V.V.
        • Koehn S.L.
        • et al.
        Loss of receptor-mediated lipid uptake via scavenger receptor A or CD36 pathways does not ameliorate atherosclerosis in hyperlipidemic mice.
        J Clin Invest. 2005; 115: 2192-2201
        • Hoebe K.
        • Georgel P.
        • Rutschmann S.
        • et al.
        CD36 is a sensor of diacylglycerides.
        Nature. 2005; 433: 523-527
        • Marleau S.
        • Harb D.
        • Bujold K.
        • et al.
        EP 80317, a ligand of the CD36 scavenger receptor, protects apolipoprotein E-deficient mice from developing atherosclerotic lesions.
        FASEB J. 2005; 19: 1869-1871
        • Frank P.G.
        • Lee H.
        • Park D.S.
        • Tandon N.N.
        • Scherer P.E.
        • Lisanti M.P.
        Genetic ablation of caveolin-1 confers protection against atherosclerosis.
        Arterioscler Thromb Vasc Biol. 2004; 24: 98-105
        • Dressman J.
        • Kincer J.
        • Matveev S.V.
        • et al.
        HIV protease inhibitors promote atherosclerotic lesion formation independent of dyslipidemia by increasing CD36-dependent cholesteryl ester accumulation in macrophages.
        J Clin Invest. 2003; 111: 389-397
        • Li A.C.
        • Brown K.K.
        • Silvestre M.J.
        • Willson T.M.
        • Palinski W.
        • Glass C.K.
        Peroxisome proliferator-activated receptor gamma ligands inhibit development of atherosclerosis in LDL receptor-deficient mice.
        J Clin Invest. 2000; 106: 523-531
        • Chawla A.
        • Boisvert W.A.
        • Lee C.H.
        • et al.
        A PPAR gamma-LXR-ABCA1 pathway in macrophages is involved in cholesterol efflux and atherogenesis.
        Mol Cell. 2001; 7: 161-171