Conditional Disruption of the Peroxisome Proliferator-Activated Receptor γ Gene in Mice Results in Lowered Expression of ABCA1, ABCG1, and apoE in Macrophages and Reduced Cholesterol Efflux

REFERENCES

• Babaev, V. R., S. Fazio, L. A. Gleaves, K. J. Carter, C. F. Semenkovich, and M. F. Linton. 1999. Macrophage lipoprotein lipase promotes foam cell formation and atherosclerosis in vivo. J. Clin. Investig. 103: 1697–1705.
   PubMedGoogle Scholar
• Babaev, V. R., M. B. Patel, C. F. Semenkovich, S. Fazio, and M. F. Linton. 2000. Macrophage lipoprotein lipase promotes foam cell formation and atherosclerosis in low density lipoprotein receptor-deficient mice. J. Biol. Chem. 275: 26293–26299.
   PubMedGoogle Scholar
• Barak, Y., M. C. Nelson, E. S. Ong, Y. Z. Jones, P. Ruiz-Lozano, K. R. Chien, A. Koder, and R. M. Evans. 1999. PPARγ is required for placental, cardiac, and adipose tissue development. Mol. Cell 4: 585–595.
   PubMed Web of Science ®Google Scholar
• Basheeruddin, K., C. Rechtoris, and T. Mazzone. 1992. Transcriptional and post-transcriptional control of apolipoprotein E gene expression in differentiating human monocytes. J. Biol. Chem. 267: 1219–1224.
   PubMedGoogle Scholar
• Basu, S. K., J. L. Goldstein, and M. S. Brown. 1983. Independent pathways for secretion of cholesterol and apolipoprotein E by macrophages. Science 219: 871–873.
   PubMedGoogle Scholar
• Basu, S. K., Y. K. Ho, M. S. Brown, D. W. Bilheimer, R. G. Anderson, and J. L. Goldstein. 1982. Biochemical and genetic studies of the apoprotein E secreted by mouse macrophages and human monocytes. J. Biol. Chem. 257: 9788–9795.
   PubMed Web of Science ®Google Scholar
• Bellosta, S., R. W. Mahley, D. A. Sanan, J. Murata, D. L. Newland, J. M. Taylor, and R. E. Pitas. 1995. Macrophage-specific expression of human apolipoprotein E reduces atherosclerosis in hypercholesterolemic apolipoprotein E-null mice. J. Clin. Investig. 96: 2170–2179.
   PubMedGoogle Scholar
• Berliner, J. A., M. Navab, A. M. Fogelman, J. S. Frank, L. L. Demer, P. A. Edwards, A. D. Watson, and A. J. Lusis. 1995. Atherosclerosis: basic mechanisms. Oxidation, inflammation, and genetics. Circulation 91: 2488–2496.
   PubMed Web of Science ®Google Scholar
• Bodzioch, M., E. Orso, J. Klucken, T. Langmann, A. Bottcher, W. Diederich, W. Drobnik, S. Barlage, C. Buchler, M. Porsch-Ozcurumez, W. E. Kaminski, H. W. Hahmann, K. Oette, G. Rothe, C. Aslanidis, K. J. Lackner, and G. Schmitz. 1999. The gene encoding ATP-binding cassette transporter 1 is mutated in Tangier disease. Nat. Genet. 22: 347–351.
   PubMed Web of Science ®Google Scholar
• Boisvert, W. A., J. Spangenberg, and L. K. Curtiss. 1995. Treatment of severe hypercholesterolemia in apolipoprotein E-deficient mice by bone marrow transplantation. J. Clin. Investig. 96: 1118–1124.
   PubMed Web of Science ®Google Scholar
• Brockman, J. A., R. A. Gupta, and R. N. Dubois. 1998. Activation of PPARγ leads to inhibition of anchorage-independent growth of human colorectal cancer cells. Gastroenterology 115: 1049–1055.
   PubMed Web of Science ®Google Scholar
• Brooks-Wilson, A., M. Marcil, S. M. Clee, L. H. Zhang, K. Roomp, M. van Dam, L. Yu, C. Brewer, J. A. Collins, H. O. Molhuizen, O. Loubser, B. F. Ouelette, K. Fichter, K. J. Ashbourne-Excoffon, C. W. Sensen, S. Scherer, S. Mott, M. Denis, D. Martindale, J. Frohlich, K. Morgan, B. Koop, S. Pimstone, J. J. Kastelein, and M. R. Hayden. 1999. Mutations in ABC1 in Tangier disease and familial high-density lipoprotein deficiency. Nat. Genet. 22: 336–345.
   PubMed Web of Science ®Google Scholar
• Chang, K. C., G. Goldspink, and J. Lida. 1990. Studies in the in vivo expression of the influenza resistance gene Mx by in-situ hybridization. Arch. Virol. 110: 151–164.
   PubMedGoogle Scholar
• Chang, T. H., and E. Szabo. 2000. Induction of differentiation and apoptosis by ligands of peroxisome proliferator-activated receptor gamma in non-small cell lung cancer. Cancer Res. 60: 1129–1138.
   PubMed Web of Science ®Google Scholar
• Chawla, A., Y. Barak, L. Nagy, D. Liao, P. Tontonoz, and R. M. Evans. 2001. PPAR-gamma dependent and independent effects on macrophage-gene expression in lipid metabolism and inflammation. Nat. Med. 7: 48–52.
   PubMed Web of Science ®Google Scholar
• Chawla, A., W. A. Boisvert, C. H. Lee, B. A. Laffitte, Y. Barak, S. B. Joseph, D. Liao, L. Nagy, P. A. Edwards, L. K. Curtiss, R. M. Evans, and P. Tontonoz. 2001. A PPARγ-LXR-ABCA1 pathway in macrophages is involved in cholesterol efflux and atherogenesis. Mol. Cell 7: 161–171.
   PubMed Web of Science ®Google Scholar
• Chen, F., S. W. Law, and B. W. O'Malley. 1993. Identification of two mPPAR-related receptors and evidence for the existence of five subfamily members. Biochem. Biophys. Res. Commun. 196: 671–677.
   PubMedGoogle Scholar
• Chinetti, G., S. Lestavel, V. Bocher, A. T. Remaley, B. Neve, I. P. Torra, E. Teissier, A. Minnich, M. Jaye, N. Duverger, H. B. Brewer, J. C. Fruchart, V. Clavey, and B. Staels. 2001. PPAR-α and PPAR-γ activators induce cholesterol removal from human macrophage foam cells through stimulation of the ABCA1 pathway. Nat. Med. 7: 53–58.
   PubMed Web of Science ®Google Scholar
• Clark, R. B., D. Bishop-Bailey, T. Estrada-Hernandez, T. Hla, L. Puddington, and S. J. Padula. 2001. The nuclear receptor PPAR gamma and immunoregulation: PPAR gamma mediates inhibition of helper T cell responses. J. Immunol. 164: 1364–1371.
   Google Scholar
• Claudel, T., M. D. Leibowitz, C. Fievet, A. Tailleux, B. Wagner, J. J. Repa, G. Torpier, J. M. Lobaccaro, J. R. Paterniti, D. J. Mangelsdorf, R. A. Heyman, and J. Auwerx. 2001. Reduction of atherosclerosis in apolipoprotein E knockout mice by activation of the retinoid X receptor. Proc. Natl. Acad. Sci. USA 98: 2610–2615.
   PubMed Web of Science ®Google Scholar
• Costet, P., Y. Luo, N. Wang, and A. R. Tall. 2000. Sterol-dependent transactivation of the ABC1 promoter by the liver X receptor/retinoid X receptor. J. Biol. Chem. 275: 28240–28245.
   PubMed Web of Science ®Google Scholar
• Cullen, P., A. Cignarella, B. Brennhausen, S. Mohr, G. Assmann, and A. von Eckardstein. 1998. Phenotype-dependent differences in apolipoprotein E metabolism and in cholesterol homeostasis in human monocyte-derived macrophages. J. Clin. Investig. 101: 1670–1677.
   PubMed Web of Science ®Google Scholar
• de Villiers, W. J., I. P. Fraser, D. A. Hughes, A. G. Doyle, and S. Gordon. 1994. Macrophage-colony-stimulating factor selectively enhances macrophage scavenger receptor expression and function. J. Exp. Med. 180: 705–709.
   PubMedGoogle Scholar
• Dory, L. 1989. Synthesis and secretion of apoE in thioglycolate-elicited mouse peritoneal macrophages: effect of cholesterol efflux. J. Lipid Res. 30: 809–816.
   PubMedGoogle Scholar
• Elstner, E., C. Muller, K. Koshizuka, E. A. Williamson, D. Park, H. Asou, P. Shintaku, J. W. Said, D. Heber, and H. P. Koeffler. 1998. Ligands for peroxisome proliferator-activated receptor gamma and retinoic acid receptor inhibit growth and induce apoptosis of human breast cancer cells in vitro and in BNX mice. Proc. Natl. Acad. Sci. USA 95: 8806–8811.
   PubMed Web of Science ®Google Scholar
• Fazio, S., V. R. Babaev, A. B. Murray, A. H. Hasty, K. J. Carter, L. A. Gleaves, J. B. Atkinson, and M. F. Linton. 1997. Increased atherosclerosis in mice reconstituted with apolipoprotein E null macrophages. Proc. Natl. Acad. Sci. USA 94: 4647–4652.
   PubMed Web of Science ®Google Scholar
• Feng, J., J. Han, S. F. Pearce, R. L. Silverstein, A. M. J. Gotto, D. P. Hajjar, and A. C. Nicholson. 2000. Induction of CD36 expression by oxidized LDL and IL-4 by a common signaling pathway dependent on protein kinase C and PPAR-γ. J. Lipid Res. 41: 688–696.
   PubMedGoogle Scholar
• Forman, B. M., J. Chen, and R. M. Evans. 1997. Hypolipidemic drugs, polyunsaturated fatty acids, and eicosanoids are ligands for peroxisome proliferator-activated receptors α and δ. Proc. Natl. Acad. Sci. USA 94: 4312–4317.
   PubMed Web of Science ®Google Scholar
• Forman, B. M., P. Tontonoz, J. Chen, R. P. Brun, B. M. Spiegelman, and R. M. Evans. 1995. 15-Deoxy-Δ12,14-prostaglandin J2 is a ligand for the adipocyte determination factor PPARγ. Cell 83: 803–812.
   PubMed Web of Science ®Google Scholar
• Ghazzi, M. N., J. E. Perez, T. K. Antonucci, J. H. Driscoll, S. M. Huang, B. W. Faja, R. W. Whitcomb, and the Troglitazone Study Group. 1997. Cardiac and glycemic benefits of troglitazone treatment in NIDDM. Diabetes 46: 433–439.
   PubMed Web of Science ®Google Scholar
• Hayhurst, G. P., Y. H. Lee, G. Lambert, J. M. Ward, and F. J. Gonzalez. 2001. Hepatocyte nuclear factor 4α (nuclear receptor 2A1) is essential for maintenance of hepatic gene expression and lipid homeostasis. Mol. Cell. Biol. 21: 1393–1403.
   PubMed Web of Science ®Google Scholar
• Hobbs, H. H., and D. J. Rader. 1999. ABC1: connecting yellow tonsils, neuropathy, and very low HDL. J. Clin. Investig. 104: 1015–1017.
   PubMed Web of Science ®Google Scholar
• Huh, H. Y., S. F. Pearce, L. M. Yesner, J. L. Schindler, and R. L. Silverstein. 1996. Regulated expression of CD36 during monocyte-to-macrophage differentiation: potential role of CD36 in foam cell formation. Blood 87: 2020–2028.
   PubMed Web of Science ®Google Scholar
• Imai, T., M. Jiang, P. Chambon, and D. Metzger. 2001. Impaired adipogenesis and lipolysis in the mouse upon selective ablation of the retinoid X receptor alpha mediated by a tamoxifen-inducible chimeric Cre recombinase (Cre-ERT2) in adipocytes. Proc. Natl. Acad. Sci. USA 98: 224–228.
   PubMed Web of Science ®Google Scholar
• Kintscher, U., S. Goetze, S. Wakino, S. Kim, S. Nagpal, R. A. Chandraratna, K. Graf, E. Fleck, W. A. Hsueh, and R. E. Law. 2000. Peroxisome proliferator-activated receptor and retinoid X receptor ligands inhibit monocyte chemotactic protein-1-directed migration of monocytes. Eur. J. Pharmacol. 401: 259–270.
   PubMedGoogle Scholar
• Kirchgessner, T. G., K. L. Svenson, A. J. Lusis, and M. C. Schotz. 1987. The sequence of cDNA encoding lipoprotein lipase. A member of a lipase gene family. J. Biol. Chem. 262: 8463–8466.
   PubMed Web of Science ®Google Scholar
• Kitamura, S., Y. Miyazaki, Y. Shinomura, S. Kondo, S. Kanayama, and Y. Matsuzawa. 1999. Peroxisome proliferator-activated receptor gamma induces growth arrest and differentiation markers of human colon cancer cells. Jpn. J. Cancer Res. 90: 75–80.
   PubMedGoogle Scholar
• Kliewer, S. A., J. M. Lenhard, T. M. Willson, I. Patel, D. C. Morris, and J. M. Lehmann. 1995. A prostaglandin J2 metabolite binds peroxisome proliferator-activated receptor gamma and promotes adipocyte differentiation. Cell 83: 813–819.
   PubMed Web of Science ®Google Scholar
• Kliewer, S. A., S. S. Sundseth, S. A. Jones, P. J. Brown, G. B. Wisely, C. S. Koble, P. Devchand, W. Wahli, T. M. Willson, J. M. Lenhard, and J. M. Lehmann. 1997. Fatty acids and eicosanoids regulate gene expression through direct interactions with peroxisome proliferator-activated receptors alpha and gamma. Proc. Natl. Acad. Sci. USA 94: 4318–4323.
   PubMed Web of Science ®Google Scholar
• Klucken, J., C. Buchler, E. Orso, W. E. Kaminski, M. Porsch-Ozcurumez, G. Liebisch, M. Kapinsky, W. Diederich, W. Drobnik, M. Dean, R. Allikmets, and G. Schmitz. 2000. ABCG1 (ABC8), the human homolog of the Drosophila white gene, is a regulator of macrophage cholesterol and phospholipid transport. Proc. Natl. Acad. Sci. USA 97: 817–822.
   PubMed Web of Science ®Google Scholar
• Kruth, H. S., S. I. Skarlatos, P. M. Gaynor, and W. Gamble. 1994. Production of cholesterol-enriched nascent high density lipoproteins by human monocyte-derived macrophages is a mechanism that contributes to macrophage cholesterol efflux. J. Biol. Chem. 269: 24511–24518.
   PubMed Web of Science ®Google Scholar
• Kubota, N., Y. Terauchi, H. Miki, H. Tamemoto, T. Yamauchi, K. Komeda, S. Satoh, R. Nakano, C. Ishii, T. Sugiyama, K. Eto, Y. Tsubamoto, A. Okuno, K. Murakami, H. Sekihara, G. Hasegawa, M. Naito, Y. Toyoshima, S. Tanaka, K. Shiota, T. Kitamura, T. Fujita, O. Ezaki, S. Aizawa, and T. Kadowaki. 1999. PPAR gamma mediates high-fat diet-induced adipocyte hypertrophy and insulin resistance. Mol. Cell 4: 597–609.
   PubMed Web of Science ®Google Scholar
• Kubota, T., K. Koshizuka, E. A. Williamson, H. Asou, J. W. Said, S. Holden, I. Miyoshi, and H. P. Koeffler. 1998. Ligand for peroxisome proliferator-activated receptor gamma (troglitazone) has potent antitumor effect against human prostate cancer both in vitro and in vivo. Cancer Res. 58: 3344–3352.
   PubMed Web of Science ®Google Scholar
• Kuhn, R., F. Schwenk, M. Aguet, and K. Rajewsky. 1995. Inducible gene targeting in mice. Science 269: 1427–1429.
   PubMed Web of Science ®Google Scholar
• Laffitte, B. A., J. J. Repa, S. B. Joseph, D. C. Wilpitz, H. R. Kast, D. J. Mangelsdorf, and P. Tontonoz. 2001. LXRs control lipid-inducible expression of the apolipoprotein E gene in macrophages and adipocytes. Proc. Natl. Acad. Sci. USA 98: 507–512.
   PubMed Web of Science ®Google Scholar
• Lakso, M., J. G. Pichel, J. R. Gorman, B. Sauer, Y. Okamoto, E. Lee, F. W. Alt, and H. Westphal. 1996. Efficient in vivo manipulation of mouse genomic sequences at the zygote stage. Proc. Natl. Acad. Sci. USA 93: 5860–5865.
   PubMed Web of Science ®Google Scholar
• Langer, C., Y. Huang, P. Cullen, B. Wiesenhutter, R. W. Mahley, G. Assmann, and A. von Eckardstein. 2000. Endogenous apolipoprotein E modulates cholesterol efflux and cholesteryl ester hydrolysis mediated by high-density lipoprotein-3 and lipid-free apolipoproteins in mouse peritoneal macrophages. J. Mol. Med. 78: 217–227.
   PubMedGoogle Scholar
• Law, R. E., S. Goetze, X. P. Xi, S. Jackson, Y. Kawano, L. Demer, M. C. Fishbein, W. P. Meehan, and W. A. Hsueh. 2000. Expression and function of PPARγ in rat and human vascular smooth muscle cells. Circulation 101: 1311–1318.
   PubMed Web of Science ®Google Scholar
• Law, R. E., W. P. Meehan, X. P. Xi, K. Graf, D. A. Wuthrich, W. Coats, D. Faxon, and W. A. Hsueh. 1996. Troglitazone inhibits vascular smooth muscle cell growth and intimal hyperplasia. J. Clin. Investig. 98: 1897–1905.
   PubMed Web of Science ®Google Scholar
• Lawn, R. M., D. P. Wade, M. R. Garvin, X. Wang, K. Schwartz, J. G. Porter, J. J. Seilhamer, A. M. Vaughan, and J. F. Oram. 1999. The Tangier disease gene product ABC1 controls the cellular apolipoprotein-mediated lipid removal pathway. J. Clin. Investig. 104: R25–R31.
   PubMed Web of Science ®Google Scholar
• Lehmann, J. M., L. B. Moore, T. A. Smith-Oliver, W. O. Wilkison, T. M. Willson, and S. A. Kliewer. 1995. An antidiabetic thiazolidinedione is a high-affinity ligand for peroxisome proliferator-activated receptor gamma (PPARγ). J. Biol. Chem. 270: 12953–12956.
   PubMed Web of Science ®Google Scholar
• Linton, M. F., J. B. Atkinson, and S. Fazio. 1995. Prevention of atherosclerosis in apolipoprotein E-deficient mice by bone marrow transplantation. Science 267: 1034–1037.
   PubMed Web of Science ®Google Scholar
• Marx, N., G. Sukhova, C. Murphy, P. Libby, and J. Plutzky. 1998. Macrophages in human atheroma contain PPARγ: differentiation-dependent peroxisomal proliferator-activated receptor gamma (PPARγ) expression and reduction of MMP-9 activity through PPARγ activation in mononuclear phagocytes in vitro. Am. J. Pathol. 153: 17–23.
   PubMed Web of Science ®Google Scholar
• Mazzone, T., and C. Reardon. 1994. Expression of heterologous human apolipoprotein E by J774 macrophages enhances cholesterol efflux to HDL3. J. Lipid Res. 35: 1345–1353.
   PubMed Web of Science ®Google Scholar
• Minamikawa, J., M. Yamauchi, D. Inoue, and H. Koshiyama. 1998. Another potential use of troglitazone in noninsulin-dependent diabetes mellitus. J. Clin. Endocrinol. Metab. 83: 1041–1042.
   PubMedGoogle Scholar
• Moore, K. J., E. D. Rosen, M. L. Fitzgerald, F. Randow, L. P. Andersson, D. Altshuler, D. S. Milstone, R. M. Mortensen, B. M. Spiegelman, and M. W. Freeman. 2001. The role of PPAR-γ in macrophage differentiation and cholesterol uptake. Nat. Med. 7: 41–47.
   PubMed Web of Science ®Google Scholar
• Mueller, E., P. Sarraf, P. Tontonoz, R. M. Evans, K. J. Martin, M. Zhang, C. Fletcher, S. Singer, and B. M. Spiegelman. 1998. Terminal differentiation of human breast cancer through PPARγ. Mol. Cell 1: 465–470.
   PubMed Web of Science ®Google Scholar
• Nagy, L., P. Tontonoz, J. G. Alvarez, H. Chen, and R. M. Evans. 1998. Oxidized LDL regulates macrophage gene expression through ligand activation of PPARγ. Cell 93: 229–240.
   PubMed Web of Science ®Google Scholar
• Naitoh, T., M. Kitahara, and N. Tsuruzoe. 2000. The effect of activation of peroxisome proliferator-activated receptor gamma (PPARγ) on human monocyte function: PPARγ ligands do not inhibit tumor necrosis factor-alpha release in human monocytic cell line THP-1. Cell Biol. Toxicol. 16: 131–135.
   PubMedGoogle Scholar
• Noguchi, N., H. Sakai, Y. Kato, J. Tsuchiya, Y. Yamamoto, E. Niki, H. Horikoshi, and T. Kodama. 1996. Inhibition of oxidation of low-density lipoprotein by troglitazone. Atherosclerosis 123: 227–234.
   PubMed Web of Science ®Google Scholar
• Okuno, A., H. Tamemoto, K. Tobe, K. Ueki, Y. Mori, K. Iwamoto, K. Umesono, Y. Akanuma, T. Fujiwara, H. Horikoshi, Y. Yazaki, and T. Kadowaki. 1998. Troglitazone increases the number of small adipocytes without the change of white adipose tissue mass in obese Zucker rats. J. Clin. Investig. 101: 1354–1361.
   PubMed Web of Science ®Google Scholar
• Okura, T., M. Nakamura, Y. Takata, S. Watanabe, Y. Kitami, and K. Hiwada. 2000. Troglitazone induces apoptosis via the p53 and Gadd45 pathway in vascular smooth muscle cells. Eur. J. Pharmacol. 407: 227–235.
   PubMed Web of Science ®Google Scholar
• Oram, J. F., R. M. Lawn, M. R. Garvin, and D. P. Wade. 2000. ABCA1 is the cAMP-inducible apolipoprotein receptor that mediates cholesterol secretion from macrophages. J. Biol. Chem. 275: 34508–34511.
   PubMed Web of Science ®Google Scholar
• Oram, J. F., and A. M. Vaughan. 2000. ABCA1-mediated transport of cellular cholesterol and phospholipids to HDL apolipoproteins. Curr. Opin. Lipidol. 11: 253–260.
   PubMed Web of Science ®Google Scholar
• Pasceri, V., H. D. Wu, J. T. Willerson, and E. T. Yeh. 2000. Modulation of vascular inflammation in vitro and in vivo by peroxisome proliferator-activated receptor-γ activators. Circulation 101: 235–238.
   PubMed Web of Science ®Google Scholar
• Plump, A. S., J. D. Smith, T. Hayek, K. Aalto-Setala, A. Walsh, J. G. Verstuyft, E. M. Rubin, and J. L. Breslow. 1992. Severe hypercholesterolemia and atherosclerosis in apolipoprotein E-deficient mice created by homologous recombination in ES cells. Cell 71: 343–353.
   PubMed Web of Science ®Google Scholar
• Porsch-Ozcurumez, M., T. Langmann, S. Heimerl, H. Borsukova, W. E. Kaminski, W. Drobnik, C. Honer, C. Schumacher, and G. Schmitz. 2001. The zinc finger protein 202 (ZNF202) is a transcriptional repressor of ATP binding cassette transporter A1 (ABCA1) and ABCG1 gene expression and a modulator of cellular lipid efflux. J. Biol. Chem. 276: 12427–12433.
   PubMed Web of Science ®Google Scholar
• Raabe, M., M. M. Veniant, M. A. Sullivan, C. H. Zlot, J. Bjorkegren, L. B. Nielsen, J. S. Wong, R. L. Hamilton, and S. G. Young. 1999. Analysis of the role of microsomal triglyceride transfer protein in the liver of tissue-specific knockout mice. J. Clin. Investig. 103: 1287–1298.
   PubMed Web of Science ®Google Scholar
• Rajagopalan, S., X. P. Meng, S. Ramasamy, D. G. Harrison, and Z. S. Galis. 1996. Reactive oxygen species produced by macrophage-derived foam cells regulate the activity of vascular matrix metalloproteinases in vitro. Implications for atherosclerotic plaque stability. J. Clin. Investig. 98: 2572–2579.
   PubMed Web of Science ®Google Scholar
• Repa, J. J., S. D. Turley, J. A. Lobaccaro, J. Medina, L. Li, K. Lustig, B. Shan, R. A. Heyman, J. M. Dietschy, and D. J. Mangelsdorf. 2000. Regulation of absorption and ABC1-mediated efflux of cholesterol by RXR heterodimers. Science 289: 1524–1529.
   PubMed Web of Science ®Google Scholar
• Ricote, M., J. Huang, L. Fajas, A. Li, J. Welch, J. Najib, J. L. Witztum, J. Auwerx, W. Palinski, and C. K. Glass. 1998. Expression of the peroxisome proliferator-activated receptor gamma (PPARγ) in human atherosclerosis and regulation in macrophages by colony-stimulating factors and oxidized low-density lipoprotein. Proc. Natl. Acad. Sci. USA 95: 7614–7619.
   PubMed Web of Science ®Google Scholar
• Rohlmann, A., M. Gotthardt, R. E. Hammer, and J. Herz. 1998. Inducible inactivation of hepatic LRP gene by cre-mediated recombination confirms role of LRP in clearance of chylomicron remnants. J. Clin. Investig. 101: 689–695.
   PubMed Web of Science ®Google Scholar
• Rosen, E. D., P. Sarraf, A. E. Troy, G. Bradwin, K. Moore, D. S. Milstone, B. M. Spiegelman, and R. M. Mortensen. 1999. PPAR γ is required for the differentiation of adipose tissue in vivo and in vitro. Mol. Cell 4: 611–617.
   PubMed Web of Science ®Google Scholar
• Rossi, A., P. Kapahi, G. Natoli, T. Takahashi, Y. Chen, M. Karin, and M. G. Santoro. 2000. Anti-inflammatory cyclopentenone prostaglandins are direct inhibitors of IκB kinase. Nature 403: 103–108.
   PubMed Web of Science ®Google Scholar
• Rust, S., M. Rosier, H. Funke, J. Real, Z. Amoura, J. C. Piette, J. F. Deleuze, H. B. Brewer, N. Duverger, P. Denefle, and G. Assmann. 1999. Tangier disease is caused by mutations in the gene encoding ATP-binding cassette transporter 1. Nat. Genet. 22: 352–355.
   Google Scholar
• Santamarina-Fojo, S., A. T. Remaley, E. B. Neufeld, and H. B. J. Brewer. 2001. Regulation and intracellular trafficking of the ABCA1 transporter. J. Lipid Res. 42: 1339–1345.
   PubMed Web of Science ®Google Scholar
• Sarraf, P., E. Mueller, D. Jones, F. J. King, D. J. DeAngelo, J. B. Partridge, S. A. Holden, L. B. Chen, S. Singer, C. Fletcher, and B. M. Spiegelman. 1998. Differentiation and reversal of malignant changes in colon cancer through PPARγ. Nat. Med. 4: 1046–1052.
   PubMed Web of Science ®Google Scholar
• Schoonjans, K., J. Peinado-Onsurbe, A. M. Lefebvre, R. A. Heyman, M. Briggs, S. Deeb, B. Staels, and J. Auwerx. 1996. PPARα and PPARγ activators direct a distinct tissue-specific transcriptional response via a PPRE in the lipoprotein lipase gene. EMBO J. 15: 5336–5348.
   PubMed Web of Science ®Google Scholar
• Schwartz, K., R. M. Lawn, and D. P. Wade. 2000. ABC1 gene expression and ApoA-I-mediated cholesterol efflux are regulated by LXR. Biochem. Biophys. Res. Commun. 274: 794–802.
   PubMed Web of Science ®Google Scholar
• Shinohara, E., S. Kihara, N. Ouchi, T. Funahashi, T. Nakamura, S. Yamashita, K. Kameda-Takemura, and Y. Matsuzawa. 1998. Troglitazone suppresses intimal formation following balloon injury in insulin-resistant Zucker fatty rats. Atherosclerosis 136: 275–279.
   PubMed Web of Science ®Google Scholar
• Spiegelman, B. M. 1997. Peroxisome proliferator-activated receptor gamma: a key regulator of adipogenesis and systemic insulin sensitivity. Eur. J. Med. Res. 2: 457–464.
   PubMedGoogle Scholar
• Spiegelman, B. M., E. Hu, J. B. Kim, and R. Brun. 1997. PPARγ and the control of adipogenesis. Biochimie 79: 111–112.
   PubMed Web of Science ®Google Scholar
• Staeheli, P., P. Danielson, O. Haller, and J. G. Sutcliffe. 1986. Transcriptional activation of the mouse Mx gene by type I interferon. Mol. Cell. Biol. 6: 4770–4774.
   PubMedGoogle Scholar
• Straus, D. S., G. Pascual, M. Li, J. S. Welch, M. Ricote, C. H. Hsiang, L. L. Sengchanthalangsy, G. Ghosh, and C. K. Glass. 2000. 15-Deoxy-Δ12,14-prostaglandin J2 inhibits multiple steps in the NF-κB signaling pathway. Proc. Natl. Acad. Sci. USA 97: 4844–4849.
   PubMed Web of Science ®Google Scholar
• Suzuki, H., Y. Kurihara, M. Takeya, N. Kamada, M. Kataoka, K. Jishage, O. Ueda, H. Sakaguchi, T. Higashi, T. Suzuki, Y. Takashima, Y. Kawabe, O. Cynshi, Y. Wada, M. Honda, H. Kurihara, H. Aburatani, T. Doi, A. Matsumoto, S. Azuma, T. Noda, Y. Toyoda, H. Itakura, Y. Yazaki, and T. Kodama. 1997. A role for macrophage scavenger receptors in atherosclerosis and susceptibility to infection. Nature 386: 292–296.
   PubMed Web of Science ®Google Scholar
• Tangirala, R. K., D. Pratico, G. A. FitzGerald, S. Chun, K. Tsukamoto, C. Maugeais, D. C. Usher, E. Pure, and D. J. Rader. 2001. Reduction of isoprostanes and regression of advanced atherosclerosis by apolipoprotein E. J. Biol. Chem. 276: 261–266.
   Google Scholar
• Tontonoz, P., L. Nagy, J. G. Alvarez, V. A. Thomazy, and R. M. Evans. 1998. PPARγ promotes monocyte/macrophage differentiation and uptake of oxidized LDL. Cell 93: 241–252.
   PubMed Web of Science ®Google Scholar
• Tontonoz, P., S. Singer, B. M. Forman, P. Sarraf, J. A. Fletcher, C. D. Fletcher, R. P. Brun, E. Mueller, S. Altiok, H. Oppenheim, R. M. Evans, and B. M. Spiegelman. 1997. Terminal differentiation of human liposarcoma cells induced by ligands for peroxisome proliferator-activated receptor gamma and the retinoid X receptor. Proc. Natl. Acad. Sci. USA 94: 237–241.
   PubMed Web of Science ®Google Scholar
• Vaidya, S., E. P. Somers, S. D. Wright, P. A. Detmers, and V. S. Bansal. 1999. 15-Deoxy-Δ12,14-prostaglandin J2 inhibits the β2 integrin-dependent oxidative burst: involvement of a mechanism distinct from peroxisome proliferator-activated receptor gamma ligation. J. Immunol. 163: 6187–6192.
   PubMedGoogle Scholar
• Van Eck, M., R. Zimmermann, P. H. Groot, R. Zechner, and T. J. Van Berkel. 2000. Role of macrophage-derived lipoprotein lipase in lipoprotein metabolism and atherosclerosis. Arterioscler. Thromb. Vasc. Biol. 20: E53–E62.
   PubMedGoogle Scholar
• Venkateswaran, A., B. A. Laffitte, S. B. Joseph, P. A. Mak, D. C. Wilpitz, P. A. Edwards, and P. Tontonoz. 2000. Control of cellular cholesterol efflux by the nuclear oxysterol receptor LXRα. Proc. Natl. Acad. Sci. USA 97: 12097–12102.
   PubMed Web of Science ®Google Scholar
• Venkateswaran, A., J. J. Repa, J. M. Lobaccaro, A. Bronson, D. J. Mangelsdorf, and P. A. Edwards. 2000. Human white/murine ABC8 mRNA levels are highly induced in lipid-loaded macrophages. A transcriptional role for specific oxysterols. J. Biol. Chem. 275: 14700–14707.
   PubMed Web of Science ®Google Scholar
• Willoughby, D. A., A. R. Moore, and P. R. Colville-Nash. 2000. Cyclopentenone prostaglandins-new allies in the war on inflammation. Nat. Med. 6: 137–138.
   PubMed Web of Science ®Google Scholar
• Witztum, J. L. 1994. The oxidation hypothesis of atherosclerosis. Lancet 344: 793–795.
   PubMed Web of Science ®Google Scholar
• Yesner, L. M., H. Y. Huh, S. F. Pearce, and R. L. Silverstein. 1996. Regulation of monocyte CD36 and thrombospondin-1 expression by soluble mediators. Arterioscler. Thromb. Vasc. Biol. 16: 1019–1025.
   PubMed Web of Science ®Google Scholar
• Zhang, S. H., R. L. Reddick, J. A. Piedrahita, and N. Maeda. 1992. Spontaneous hypercholesterolemia and arterial lesions in mice lacking apolipoprotein E. Science 258: 468–471.
   Google Scholar
• Zhang, W. Y., P. M. Gaynor, and H. S. Kruth. 1996. Apolipoprotein E produced by human monocyte-derived macrophages mediates cholesterol efflux that occurs in the absence of added cholesterol acceptors. J. Biol. Chem. 271: 28641–28646.
   PubMed Web of Science ®Google Scholar