Role of CD36, the Macrophage Class B Scavenger Receptor, in Atherosclerosis
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1 Role of CD36, the Macrophage Class B Scavenger Receptor, in Atherosclerosis ANDREW C. NICHOLSON, JIHONG HAN, MARIA FEBBRAIO, ROY L. SILVERSTERIN, AND DAVID P. HAJJAR Center of Vascular Biology, Cornell University Medical College, New York, New York 10021, USA ABSTRACT: Recent work in the field of atherosclerosis has greatly expanded our knowledge of the pathogenesis of this disease. Scavenger receptors, including CD36, are thought to be most important early in the disease progression during macrophage uptake of modified LDL and foam cell formation. Genetically engineered murine models have been used to elucidate the contribution of the different scavenger receptors, to identify specific ligands related to LDL modifications, and to assess the possible therapeutic ramifications of targeting scavenger receptors. We have demonstrated a major role for CD36 in macrophage foam cell development and subsequent lesion development in vivo. Absence of CD36 in an atherogenic Apo E null background resulted in a 70% decrease in total lesion area in Western diet-fed mice. We have also made significant progress in our understanding of the regulation of expression of CD36 and have demonstrated that OxLDL can stimulate its own uptake by induction of CD36 gene expression. The mechanism by which OxLDL upregulates CD36 involves activation of the transcription factor, PPAR-. KEYWORDS: atherosclerosis; CD36; scavenger receptors; macrophages Considerable experimental work has illuminated pathways of LDL oxidation in the vessel wall, and preventive strategies in animal models and humans based on antioxidant therapy are ongoing and show promise. Several cellular receptors involved in binding and internalizing modified LDL particles (including OxLDL) have been identified and are termed scavenger receptors. Although their physiological roles are unclear, they presumably have a significant role in atherosclerotic foam cell development. 1 4 LDL particles are presumably subjected to oxidative modification in the vessel wall by reactive oxygen metabolites produced by monocytes, neutrophils, and other cells in the developing lesion. 5 The competitive inhibition of AcLDL binding by Ox- LDL, however, was only partial. Subsequent binding and cross competition studies with both OxLDL and AcLDL in macrophages and numerous transfected and normal cell lines have clearly demonstrated the existence of multiple scavenger receptor Address for correspondence: David P. Hajjar, Ph.D., Weill Medical College of Cornell University, Department of Pathology, A-626, 1300 York Avenue, New York, NY Voice: ; fax: dphajjar@mail.med.cornell.edu 224 转载
2 NICHOLSON et al.: CD36 IN ATHEROSCLEROSIS 225 functional classes, 6 8 including receptor(s) for AcLDL, receptor(s) for OxLDL, and receptor(s) that recognize both. Since type I and type II receptors exhibit identical binding specificity, it does not appear that differences at the C terminus account for differences in ligand recognition. 8 Steinberg and his colleagues recently showed that oxidatively damaged erythrocytes bind to macrophages and that OxLDL, but not AcLDL or native LDL, blocks this binding, 9 providing further evidence for a receptor other than the cloned type I/II receptor for oxidized lipid on the macrophage surface. They subsequently showed that this receptor is identical to macrosialin, the mouse homologue of CD Because of the importance of OxLDL in the pathogenesis of atherosclerosis and the data suggesting that the type I/II receptor cannot account for most OxLDL binding to macrophages and vascular cells, considerable efforts have been taken to identify other scavenger receptors. Endemann and her colleagues 11 used an expression cloning strategy to identify murine macrophage receptors that recognized OxLDL but not AcLDL. They identified one such receptor that encoded the murine homologue of CD36 (platelet gpiv), 11 an 88-kD transmembrane glycoprotein. CD36 is now referred to as a type B scavenger receptor. It is a member of a family of receptors which also includes SR-B1/CLA-1, an HDL receptor CD36 is expressed by monocyte/macrophages, 15 platelets, 16 microvascular endothelial cells, 17 and adipose tissue. 18 Like type A scavenger receptors, 19 CD36 recognizes a broad variety of ligands including OxLDL, 11,20 anionic phospholipids, 21 apoptotic cells, 22 thrombospondin (TSP), 23 collagen, 24 Plasmodium falciparum-infected erythrocytes, 25 and long-chain fatty acids. 18 Unlike class A receptors, which recognize the oxidized apoprotein portion of the lipoprotein particle, 26 CD36 binds to the lipid moiety of OxLDL. 20 Binding of OxLDL to CD36-transfected cells is inhibited by anionic phospholipid vesicles. 21 CD36 also binds HDL; 27 however, SR-BI mediates uptake of HDL CE with much greater efficiency than does CD Recently, CD36 was also identified as the major receptor for LDL modified by monocyte-generated reactive nitrogen species. 29 CD36-transfected cells bind OxLDL in a saturable manner. Binding, internalization, and degradation of OxLDL is increased fourfold in CD36-transfected cells relative to cells transfected with vector alone. 20 More than half the binding of OxLDL by human monocyte-derived macrophages is inhibited by anti-cd36 antibodies. 20 In our experiments, LDL and acetylated LDL (AcLDL) bind equivalently to control and CD36-transfected cells. 20 However, others have reported that CD36 will bind native LDL. 27 Expression of CD36 in monocyte/macrophages depends on both the differentiation state as well as exposure to soluble mediators. 30,31 We studied the effect of lipoproteins, native LDL, and modified LDL (AcLDL and OxLDL) on the expression of CD36 in J774 cells, a murine macrophage cell line. 32 Exposure to lipoproteins resulted in a marked induction of CD36 mrna expression (four- to eightfold). Maximum induction was observed 2 hours after treatment with AcLDL and at 4 hours after LDL and OxLDL. Expression of CD36 mrna persisted throughout 24 hours with each treatment group. Induction of CD36 mrna expression also led to an increase in CD36 protein, with the greatest induction by OxLDL (fourfold). In the presence of actinomycin D, treatment of macrophages with LDL, AcLDL, or OxLDL did not affect CD36 mrna stability, implying that CD36 mrna was transcriptionally regulated by lipoproteins. 32
3 226 ANNALS NEW YORK ACADEMY OF SCIENCES Induction of CD36 by OxLDL is due to its ability to activate the transcription factor PPAR-γ (peroxisome proliferator activated receptor-γ). 33,34 PPAR-γ is a member of a nuclear hormone superfamily that can heterodimerize with the retinoid X receptor (RXR). These proteins are transcriptional regulators of genes encoding proteins involved in adipogenesis and lipid metabolism. 35 Other PPAR-γ ligands (15- deoxy 12,14 prostaglandin J2 (15d-PGJ2), and the thiazolidinedione class of antidiabetic drugs) also increase CD36 expression. 33,34 These results further imply that macrophage expression of CD36 and foam cell formation in atherosclerotic lesions may be perpetuated by a cycle in which lipids continue to drive expression of a lipoprotein receptor in a self-regulatory manner. Phorbol esters (PMA), M-CSF, and IL-4 have also been shown to increase monocyte/macrophage expression of CD36, 31 whereas expression of CD36 is downregulated in response to cholesterol efflux, 36 lipopolysaccharide, 31 dexamethasone, 31 and interferon-γ. 37 With the exception of OxLDL, which activates PPAR-γ leading to CD36 gene transcription, the mechanism(s) by which this diverse collection of factors modulates CD36 expression remains undefined. Transforming growth factorβ1 (TGF-β1) and TGF-β2 are multifunctional mediators that regulate cellular growth, migration, adhesion, extracellular matrix formation, and apoptosis. 38 We investigated the effect of transforming growth factor-β1 (TGF-β1) and TGF-β2 on the expression of CD36 in macrophages. Treatment of PMA-differentiated THP-1 macrophages with TGF-β decreased expression of CD36 mrna and surface protein. TGF-β also inhibited CD36 mrna expression induced by PPAR-γ ligands, Ox- LDL, and 15-deoxy 12,14 prostaglandin J 2, suggesting that TGF-β downregulated CD36 expression by inactivating PPAR-γ mediated signaling. TGF-β increased phosphorylation of both MAP kinase (MAPK) and PPAR-γ, whereas MAPK inhibitors reversed suppression of CD36 and inhibited PPAR-γ phosphorylation induced by TGF-β. MAPK inhibitors alone increased expression of CD36 mrna and protein but had no effect on PPAR-γ protein levels. Thus, TGF-β decreases CD36 expression by phosphorylation of MAPK, subsequent MAPK phosphorylation of PPAR-γ, and decreased CD36 transcription by phosphorylated PPAR-γ. We hypothesized that knocking out CD36 would also alter the course of atherosclerosis by delaying or preventing foam cell and fatty streak formation. To test this hypothesis, we created a mouse null in CD These mice produced no detectable CD36 protein, were viable, and bred normally. A significant decrease in binding and uptake of OxLDL lipoprotein was observed in peritoneal macrophages of null mice as compared with those from control mice. 39 This reduced binding and uptake of Ox- LDL was expected based on previous data in human macrophages. A genetic polymorphism in the CD36 gene has been identified in an Asian population 40 and shown to result in deficient expression of CD36 (NAK a- phenotype). Monocyte-derived macrophages isolated from these patients bound 40% less Ox-LDL and accumulated 40% less cholesterol ester than did cells derived from normal controls, further implicating CD36 as a physiological OxLDL receptor. 41 CD36-null mice were created by targeted homologous recombination. There was a significant decrease in binding and uptake of OxLDL in peritoneal macrophages of null mice as compared with those from control mice. To evaluate the role of CD36 in atherosclerosis, we crossed CD36 null to the atherogenic apoe null strain and assessed lesion formation. CD36-apo E double null mice (DKO) maintained on a high fat diet had 70% fewer aortic lesions, as determined by en face analysis of the aortic tree.
4 NICHOLSON et al.: CD36 IN ATHEROSCLEROSIS 227 Thus, this murine model of atherosclerosis supports the hypothesis that CD36 is a major receptor for proatherogenic lipids. However, the specific role that CD36 plays in the development of the human atheroma remains to be determined. In support of a role for CD36 in human vascular disease, lipid-laden macrophages in human atherosclerotic lesions exhibit strong immunoreactivity to CD36, but a low or moderate level of immunoreactivity to the type A scavenger receptor. 42 This high level of expression of CD36 in lipid-laden macrophages may reflect increased expression in response to OxLDL-derived PPAR-γ ligands, which, in turn, activates CD36 gene transcription. Thus, we believe that CD36 and PPAR-γ can be potential targets for therapeutic intervention to block macrophage foam cell development during atherosclerosis. REFERENCES 1. STEINBERG, D Circulation 76: STEINBERG, D., S. PARTHASARATHY, T. CAREW, et al N. Engl. J. Med. 320: GOWN, A., T. TSUKADA & R. ROSS Am. J. Pathol. 125: FOGELMAN, A., B. VAN LENTEN, C. WARDEN, et al J. Cell Sci. Suppl. 9: PALINSKI, W., M. ROSENFELD, S. YLA-HERTTUALA, et al Proc. Natl. Acad. Sci. USA 86: SPARROW, C., S. PARTHASARATHY & D. STEINBERG J. Biol. Chem. 264: ARAI, H., T. KITA, M. YOKODE, et al Biochem. Biophys. Res. Commun. 159: FREEMAN, M., Y. EKKEL, L. ROHRER, et al Proc. Natl. Acad. Sci. USA 88: SAMBRANO, G., S. PARTHASARATHY & D. STEINBERG Proc. Natl. Acad. Sci. USA 91: RAMPRASAD, M., W. FISCHER, J. WITZTUM, et al Proc. Natl. Acad. Sci. USA 92: ENDEMANN, G., L. STANTON, K. MADDEN, et al J. Biol. Chem. 268: ACTON, S., R. ATTILIO, K. LANDSCHULTZ, et al Science 271: ACTON, S., P. SCHERER, H. LODISH, et al J. Biol. Chem. 269: CALVO, D. & M.A. VEGA J. Biol. Chem. 268: TALLE, M., P. RAO, E. WESTBERG, et al Cell. Immunol. 78: LI, Y. S., Y.J. SHYY, J.G. WRIGHT, et al Mol. Cell Biochem. 126: GREENWALT, D., R. LIPSKY, C. OCKENHOUSE, et al Blood 80: ABUMRAD, N., M.R. EL-MAGHRABI, E. AMRI, et al J. Biol. Chem. 268: KRIEGER, M., S. ACTON, J. ASHKENAS, et al J. Biol. Chem. 268: NICHOLSON, A., S.F.A. PEARCE & R. SILVERSTEIN Arteriov. Thromb. 15: RIGOTTI, A., S. ACTON & M. KRIEGER J. Biol. Chem. 270: REN, Y., R. SILVERSTEIN, J. ALLEN, et al J. Exp. Med. 181: ASCH, A., J. BARNWELL, R. SILVERSTEIN, et al J. Clin. Invest. 79: TANDON, N., U. KRALISZ & G. JAMIESON J. Biol. Chem. 264: BARNWELL, J., C. OCKENHOUSE & D. KNOWLES J. Immunol. 135: PARTHASARATHY, S., L. FONG, D. OTERO, et al Proc. Natl. Acad. Sci. USA 84: CALVO, D., D. GOMEZ-CORONADO, Y. SUAREZ, et al J. Lipid Res. 39: CONNELLY, M.A., S. KLEIN, S. AZHAR, et al J. Biol. Chem. 274: PODREZ, E.A., M. FEBBRAIO, N. SHEIBANI, et al J. Clin. Invest. 105:
5 228 ANNALS NEW YORK ACADEMY OF SCIENCES 30. HUH, H.Y., S.F.A. PEARCE, L. YESNER, et al Blood 87: YESNER, L., H. HUH, S.F.A. PEARCE, et al Arterio. and Thromb. 16: HAN, J., D.P. HAJJAR, M. FEBBRAIO, et al J. Biol. Chem. 272: TONTONOZ, P., L. NAGY, J. ALVAREZ, et al Cell 93: NAGY, L., P. TONTONOZ, J. ALVAREZ, et al Cell 93: TONTONOZ, P., E. HU, & B. SPIEGELMAN Curr. Opin. Genet. Dev. 5: HAN, J., D.P. HAJJAR, J.M. TAURAS, et al J. Lipid Res. 40: NAKAGAWA, T., S. NOZAKI, M. NISHIDA, et al Arterioscler. Thromb. Vasc. Biol. 18: SPORN, M., A. ROBERTS, L. WAKEFIELD, et al J. Cell Biol. 105: FEBBRAIO, M., N.A. ABUMRAD, D.P. HAJJAR, et al J. Biol. Chem. 274: KASHIWAGI, H., Y. TOMIYAMA, Y. KOSUGI, et al Blood 83: NOZAKI, S., H. KASHIWAGI, S. YAMASHITA, et al J. Clin. Invest. 96: NAKATA, A., Y. NAKAGAWA, M. NISHIDA, et al Arterioscler. Thromb. Vasc. Biol. 19:
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