Table of Contents Author Guidelines Submit a Manuscript
PPAR Research
Volume 2008, Article ID 285842, 7 pages
http://dx.doi.org/10.1155/2008/285842
Review Article

Peroxisome Proliferator-Activated Receptors in the Modulation of the Immune/Inflammatory Response in Atherosclerosis

Laboratorio de Hemostasia y Genética Vascular, Centro de Biofísica y Bioquímica, Instituto Venezolano de Investigaciones Científicas (I.V.I.C.), 1020 Caracas, Venezuela

Received 29 February 2008; Revised 9 May 2008; Accepted 2 August 2008

Academic Editor: Francine Gregoire

Copyright © 2008 Ana Z. Fernandez. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. R. Ross, “Atherosclerosis—an inflammatory disease,” The New England Journal of Medicine, vol. 340, no. 2, pp. 115–126, 1999. View at Publisher · View at Google Scholar
  2. G. Chinetti, J.-C. Fruchart, and B. Staels, “Peroxisome proliferator-activated receptors (PPARs): nuclear receptors at the crossroads between lipid metabolism and inflammation,” Inflammation Research, vol. 49, no. 10, pp. 497–505, 2000. View at Publisher · View at Google Scholar
  3. B. P. Neve, J.-C. Fruchart, and B. Staels, “Role of the peroxisome proliferator-activated receptors (PPAR) in atherosclerosis,” Biochemical Pharmacology, vol. 60, no. 8, pp. 1245–1250, 2000. View at Publisher · View at Google Scholar
  4. S. Cuzzocrea, B. Pisano, L. Dugo et al., “Rosiglitazone, a ligand of the peroxisome proliferator-activated receptor-γ, reduces acute inflammation,” European Journal of Pharmacology, vol. 483, no. 1, pp. 79–93, 2004. View at Publisher · View at Google Scholar
  5. R. Adamiec, M. Gacka, T. Dobosz, S. Szymaniec, D. Bednarska-Chabowska, and A. Sadakierska-Chudy, “Stimulation of the peroxisome proliferator-activated receptor γ (PPARγ) and the expression of selected blood monocyte cytokine genes in diabetic macroangiopathy,” Atherosclerosis, vol. 194, no. 2, pp. e108–e115, 2007. View at Publisher · View at Google Scholar · View at PubMed
  6. P. K. Shah, “Circulating markers of inflammation for vascular risk prediction: are they ready for prime time,” Circulation, vol. 101, no. 15, pp. 1758–1759, 2000. View at Google Scholar
  7. G. Chinetti, S. Lestavel, V. Bocher et al., “PPAR-α and PPAR-γ activators induce cholesterol removal from human macrophage foam cells through stimulation of the ABCA1 pathway,” Nature Medicine, vol. 7, no. 1, pp. 53–58, 2001. View at Publisher · View at Google Scholar · View at PubMed
  8. Y. Fan, Y. Wang, Z. Tang et al., “Suppression of pro-inflammatory adhesion molecules by PPAR-δ in human vascular endothelial cells,” Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 28, no. 2, pp. 315–321, 2008. View at Publisher · View at Google Scholar · View at PubMed
  9. H. Lee, W. Shi, P. Tontonoz et al., “Role for peroxisome proliferator-activated receptor α in oxidized phospholipid-induced synthesis of monocyte chemotactic protein-1 interleukin-8 by endothelial cells,” Circulation Research, vol. 87, no. 6, pp. 516–521, 2000. View at Google Scholar
  10. T. M. Willson, P. J. Brown, D. D. Sternbach, and B. R. Henke, “The PPARs: from orphan receptors to drug discovery,” Journal of Medicinal Chemistry, vol. 43, no. 4, pp. 527–550, 2000. View at Publisher · View at Google Scholar
  11. N. Marx, G. K. Sukhova, T. Collins, P. Libby, and J. Plutzky, “PPARα activators inhibit cytokine-induced vascular cell adhesion molecule-1 expression in human endothelial cells,” Circulation, vol. 99, no. 24, pp. 3125–3131, 1999. View at Google Scholar
  12. L. Michalik, B. Desvergne, N. S. Tan et al., “Impaired skin wound healing in peroxisome proliferator-activated receptor (PPAR)α and PPARβ mutant mice,” Journal of Cell Biology, vol. 154, no. 4, pp. 799–814, 2001. View at Publisher · View at Google Scholar · View at PubMed
  13. T. E. Akiyama, G. Lambert, C. J. Nicol et al., “Peroxisome proliferator-activated receptor β/δ regulates very low density lipoprotein production and catabolism in mice on a Western diet,” The Journal of Biological Chemistry, vol. 279, no. 20, pp. 20874–20881, 2004. View at Publisher · View at Google Scholar · View at PubMed
  14. D. W. Gilroy and P. R. Colville-Nash, “New insights into the role of COX 2 in inflammation,” Journal of Molecular Medicine, vol. 78, no. 3, pp. 121–129, 2000. View at Publisher · View at Google Scholar
  15. N. S. Tan, L. Michalik, N. Noy et al., “Critical roles of PPARβ/δ in keratinocyte response to inflammation,” Genes & Development, vol. 15, no. 24, pp. 3263–3277, 2001. View at Publisher · View at Google Scholar · View at PubMed
  16. C. Jehl-Pietri, C. Bastie, I. Gillot, S. Luquet, and P. A. Grimaldi, “Peroxisome-proliferator-activated receptor δ mediates the effects of long-chain fatty acids on post-confluent cell proliferation,” Biochemical Journal, vol. 350, no. 1, pp. 93–98, 2000. View at Publisher · View at Google Scholar
  17. U. Risérus, D. Sprecher, T. Johnson et al., “Activation of peroxisome proliferator-activated receptor (PPAR)δ promotes reversal of multiple metabolic abnormalities, reduces oxidative stress, and increases fatty acid oxidation in moderately obese men,” Diabetes, vol. 57, no. 2, pp. 332–339, 2008. View at Publisher · View at Google Scholar · View at PubMed
  18. W. R. Oliver, Jr., J. L. Shenk, M. R. Snaith et al., “A selective peroxisome proliferator-activated receptor δ agonist promotes reverse cholesterol transport,” Proceedings of the National Academy of Sciences of the United States of America, vol. 98, no. 9, pp. 5306–5311, 2001. View at Publisher · View at Google Scholar · View at PubMed
  19. M.-B. Debril, J.-P. Renaud, L. Fajas, and J. Auwerx, “The pleiotropic functions of peroxisome proliferator-activated receptor γ,” Journal of Molecular Medicine, vol. 79, no. 1, pp. 30–47, 2001. View at Publisher · View at Google Scholar
  20. J. M. Lehmann, J. M. Lenhard, B. B. Oliver, G. M. Ringold, and S. A. Kliewer, “Peroxisome proliferator-activated receptors α and γ are activated by indomethacin and other non-steroidal anti-inflammatory drugs,” The Journal of Biological Chemistry, vol. 272, no. 6, pp. 3406–3410, 1997. View at Publisher · View at Google Scholar
  21. K. Yu, W. Bayona, C. B. Kallen et al., “Differential activation of peroxisome proliferator-activated receptors by eicosanoids,” The Journal of Biological Chemistry, vol. 270, no. 41, pp. 23975–23983, 1995. View at Publisher · View at Google Scholar
  22. J. U. Scher and M. H. Pillinger, “15d-PGJ2: the anti-inflammatory prostaglandin?,” Clinical Immunology, vol. 114, no. 2, pp. 100–109, 2005. View at Publisher · View at Google Scholar · View at PubMed
  23. F. J. Schopfer, Y. Lin, P. R. S. Baker et al., “Nitrolinoleic acid: an endogenous peroxisome proliferator-activated receptor γ ligand,” Proceedings of the National Academy of Sciences of the United States of America, vol. 102, no. 7, pp. 2340–2345, 2005. View at Publisher · View at Google Scholar · View at PubMed
  24. P. R. S. Baker, Y. Lin, F. J. Schopfer et al., “Fatty acid transduction of nitric oxide signaling: multiple nitrated unsaturated fatty acid derivatives exist in human blood and urine and serve as endogenous peroxisome proliferator-activated receptor ligands,” The Journal of Biological Chemistry, vol. 280, no. 51, pp. 42464–42475, 2005. View at Publisher · View at Google Scholar · View at PubMed
  25. P. R. S. Baker, F. J. Schopfer, S. Sweeney, and B. A. Freeman, “Red cell membrane and plasma linoleic acid nitration products: synthesis, clinical identification, and quantitation,” Proceedings of the National Academy of Sciences of the United States of America, vol. 101, no. 32, pp. 11577–11582, 2004. View at Publisher · View at Google Scholar · View at PubMed
  26. R. Cunard, M. Ricote, D. DiCampli et al., “Regulation of cytokine expression by ligands of peroxisome proliferator activated receptors,” The Journal of Immunology, vol. 168, no. 6, pp. 2795–2802, 2002. View at Google Scholar
  27. A. J. Lusis, “Atherosclerosis,” Nature, vol. 407, no. 6801, pp. 233–241, 2000. View at Google Scholar
  28. K. H. Han, M. K. Chang, A. Boullier et al., “Oxidized LDL reduces monocyte CCR2 expression through pathways involving peroxisome proliferator-activated receptor γ,” The Journal of Clinical Investigation, vol. 106, no. 6, pp. 793–802, 2000. View at Publisher · View at Google Scholar · View at PubMed
  29. J. Galle, T. Hansen-Hagge, C. Wanner, and S. Seibold, “Impact of oxidized low density lipoprotein on vascular cells,” Atherosclerosis, vol. 185, no. 2, pp. 219–226, 2006. View at Publisher · View at Google Scholar · View at PubMed
  30. L. Nagy, P. Tontonoz, J. G. A. Alvarez, H. Chen, and R. M. Evans, “Oxidized LDL regulates macrophage gene expression through ligand activation of PPARγ,” Cell, vol. 93, no. 2, pp. 229–240, 1998. View at Publisher · View at Google Scholar
  31. G. Leonarduzzi, M. C. Arkan, H. Başağa, E. Chiarpotto, A. Sevanian, and G. Poli, “Lipid oxidation products in cell signaling,” Free Radical Biology and Medicine, vol. 28, no. 9, pp. 1370–1378, 2000. View at Publisher · View at Google Scholar
  32. M. Ricote, J. Huang, L. Fajas et al., “Expression of the peroxisome proliferator-activated receptor γ (PPARγ) in human atherosclerosis and regulation in macrophages by colony stimulating factors and oxidized low density lipoprotein,” Proceedings of the National Academy of Sciences of the United States of America, vol. 95, no. 13, pp. 7614–7619, 1998. View at Publisher · View at Google Scholar
  33. J. Feng, J. Han, S. F. A. Pearce et al., “Induction of CD36 expression by oxidized LDL and IL-4 by a common signaling pathway dependent on protein kinase C and PPAR-γ,” Journal of Lipid Research, vol. 41, no. 5, pp. 688–696, 2000. View at Google Scholar
  34. B. Fischer, A. von Knethen, and B. Brüne, “Dualism of oxidized lipoproteins in provoking and attenuating the oxidative burst in macrophages: role of peroxisome proliferator-activated receptor-γ,” The Journal of Immunology, vol. 168, no. 6, pp. 2828–2834, 2002. View at Google Scholar
  35. S. W. Chung, B. Y. Kang, S. H. Kim et al., “Oxidized low density lipoprotein inhibits interleukin-12 production in lipopolysaccharide-activated mouse macrophages via direct interactions between peroxisome proliferator-activated receptor-γ and nuclear factor-κB,” The Journal of Biological Chemistry, vol. 275, no. 42, pp. 32681–32687, 2000. View at Publisher · View at Google Scholar · View at PubMed
  36. R. Schreck, K. Albermann, and P. A. Baeuerle, “Nuclear factor κB: an oxidative stress-responsive transcription factor of eukaryotic cells,” Free Radical Research Communications, vol. 17, no. 4, pp. 221–237, 1992. View at Publisher · View at Google Scholar
  37. S. Schoonbroodt and J. Piette, “Oxidative stress interference with the nuclear factor-κB activation pathways,” Biochemical Pharmacology, vol. 60, no. 8, pp. 1075–1083, 2000. View at Publisher · View at Google Scholar
  38. C.-Y. Han, S.-Y. Park, and Y. K. Pak, “Role of endocytosis in the transactivation of nuclear factor-κB by oxidized low-density lipoprotein,” Biochemical Journal, vol. 350, no. 3, pp. 829–837, 2000. View at Publisher · View at Google Scholar
  39. D. T. Price and J. Loscalzo, “Cellular adhesion molecules and atherogenesis,” The American Journal of Medicine, vol. 107, no. 1, pp. 85–97, 1999. View at Publisher · View at Google Scholar
  40. N. Wang, L. Verna, N.-G. Chen et al., “Constitutive activation of peroxisome proliferator-activated receptor-γ suppresses pro-inflammatory adhesion molecules in human vascular endothelial cells,” The Journal of Biological Chemistry, vol. 277, no. 37, pp. 34176–34181, 2002. View at Publisher · View at Google Scholar · View at PubMed
  41. G. K. Hansson, A.-K. L. Robertson, and C. Söderberg-Nauclér, “Inflammation and atherosclerosis,” Annual Review of Pathology, vol. 1, no. 1, pp. 297–329, 2006. View at Publisher · View at Google Scholar · View at PubMed
  42. N. Marx, B. Kehrle, K. Kohlhammer et al., “PPAR activators as anti-inflammatory mediators in human T lymphocytes: implications for atherosclerosis and transplantation-associated arteriosclerosis,” Circulation Research, vol. 90, no. 6, pp. 703–710, 2002. View at Publisher · View at Google Scholar
  43. L. Brånén, L. Hovgaard, M. Nitulescu, E. Bengtsson, J. Nilsson, and S. Jovinge, “Inhibition of tumor necrosis factor-α reduces atherosclerosis in apolipoprotein E knockout mice,” Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 24, no. 11, pp. 2137–2142, 2004. View at Publisher · View at Google Scholar · View at PubMed
  44. S. Kurebayashi, X. Xu, S. Ishii, M. Shiraishi, H. Kouhara, and S. Kasayama, “A novel thiazolidinedione MCC-555 down-regulates tumor necrosis factor-α-induced expression of vascular cell adhesion molecule-1 in vascular endothelial cells,” Atherosclerosis, vol. 182, no. 1, pp. 71–77, 2005. View at Publisher · View at Google Scholar · View at PubMed
  45. P. Delerive, K. De Bosscher, S. Besnard et al., “Peroxisome proliferator-activated receptor α negatively regulates the vascular inflammatory gene response by negative cross-talk with transcription factors NF-κB and AP-1,” The Journal of Biological Chemistry, vol. 274, no. 45, pp. 32048–32054, 1999. View at Publisher · View at Google Scholar
  46. A. Tedgui and Z. Mallat, “Anti-inflammatory mechanisms in the vascular wall,” Circulation Research, vol. 88, no. 9, pp. 877–887, 2001. View at Publisher · View at Google Scholar
  47. C. Jiang, A. T. Ting, and B. Seed, “PPAR-γ agonists inhibit production of monocyte inflammatory cytokines,” Nature, vol. 391, no. 6662, pp. 82–86, 1998. View at Publisher · View at Google Scholar · View at PubMed
  48. A. C. Li, K. K. Brown, M. J. Silvestre, T. M. Willson, W. Palinski, and C. K. Glass, “Peroxisome proliferator-activated receptor γ ligands inhibit development of atherosclerosis in LDL receptor-deficient mice,” The Journal of Clinical Investigation, vol. 106, no. 4, pp. 523–531, 2000. View at Publisher · View at Google Scholar · View at PubMed
  49. Y. Ye, S. P. Nishi, S. Manickavasagam et al., “Activation of peroxisome proliferator-activated receptor-γ (PPAR-γ) by atorvastatin is mediated by 15-deoxy-Δ12,14-PGJ2,” Prostaglandins & Other Lipid Mediators, vol. 84, no. 1-2, pp. 43–53, 2007. View at Publisher · View at Google Scholar · View at PubMed
  50. A. von Knethen and B. Brüne, “Delayed activation of PPARγ by LPS and IFN-γ attenuates the oxidative burst in macrophages,” The FASEB Journal, vol. 15, no. 2, pp. 535–544, 2001. View at Publisher · View at Google Scholar · View at PubMed
  51. Z. Mallat, S. Besnard, M. Duriez et al., “Protective role of interleukin-10 in atherosclerosis,” Circulation Research, vol. 85, no. 8, pp. e17–e24, 1999. View at Google Scholar
  52. P. W. Thompson, A. I. Bayliffe, A. P. Warren, and J. R. Lamb, “Interleukin-10 is upregulated by nanomolar rosiglitazone treatment of mature dendritic cells and human CD4+ T cells,” Cytokine, vol. 39, no. 3, pp. 184–191, 2007. View at Publisher · View at Google Scholar · View at PubMed
  53. B. R. Kwak, S. Myit, F. Mulhaupt et al., “PPARγ but not PPARα ligands are potent repressors of major histocompatibility complex class II induction in atheroma-associated cells,” Circulation Research, vol. 90, no. 3, pp. 356–362, 2002. View at Publisher · View at Google Scholar
  54. C.-H. Lee, A. Chawla, N. Urbiztondo, D. Liao, W. A. Boisvert, and R. M. Evans, “Transcriptional repression of atherogenic inflammation: modulation by PPARδ,” Science, vol. 302, no. 5644, pp. 453–457, 2003. View at Publisher · View at Google Scholar · View at PubMed
  55. T. L. Graham, C. Mookherjee, K. E. Suckling, C. N. A. Palmer, and L. Patel, “The PPARδ agonist GW0742X reduces atherosclerosis in LDLR/ mice,” Atherosclerosis, vol. 181, no. 1, pp. 29–37, 2005. View at Publisher · View at Google Scholar · View at PubMed
  56. G. D. Barish, A. R. Atkins, M. Downes et al., “PPARδ regulates multiple proinflammatory pathways to suppress atherosclerosis,” Proceedings of the National Academy of Sciences of the United States of America, vol. 105, no. 11, pp. 4271–4276, 2008. View at Publisher · View at Google Scholar · View at PubMed
  57. Y. Takata, J. Liu, F. Yin et al., “PPARδ-mediated anti-inflammatory mechanisms inhibit angiotensin II-accelerated atherosclerosis,” Proceedings of the National Academy of Sciences of the United States of America, vol. 105, no. 11, pp. 4277–4282, 2008. View at Publisher · View at Google Scholar · View at PubMed
  58. G. Pascual, A. L. Fong, S. Ogawa et al., “A SUMOylation-dependent pathway mediates transrepression of inflammatory response genes by PPAR-γ,” Nature, vol. 437, no. 7059, pp. 759–763, 2005. View at Publisher · View at Google Scholar · View at PubMed
  59. T. Ohshima, H. Koga, and K. Shimotahno, “Transcriptional activity of peroxisome proliferator-activated receptor γ is modulated by SUMO-1 modification,” The Journal of Biological Chemistry, vol. 279, no. 28, pp. 29551–29557, 2004. View at Publisher · View at Google Scholar · View at PubMed