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Cholesterol
Volume 2011 (2011), Article ID 503028, 8 pages
http://dx.doi.org/10.1155/2011/503028
Review Article

Methotrexate in Atherogenesis and Cholesterol Metabolism

1Department of Medicine, Division of Translational Medicine, New York University School of Medicine, NBV 16N1, 550 First Avenue, New York, NY 10016, USA
2Inflammation Section, Winthrop Research Institute, Department of Medicine, Winthrop University Hospital, 222 Station Plaza North, Suite 502, Mineola, NY 11501-3893, USA

Received 15 October 2010; Revised 11 January 2011; Accepted 11 January 2011

Academic Editor: M. Jauhiainen

Copyright © 2011 Eric Coomes et al. 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. C. Meune, E. Touzé, L. Trinquart, and Y. Allanore, “High risk of clinical cardiovascular events in rheumatoid arthritis: levels of associations of myocardial infarction and stroke through a systematic review and meta-analysis,” Archives of Cardiovascular Diseases, vol. 103, no. 4, pp. 253–261, 2010. View at Publisher · View at Google Scholar · View at Scopus
  2. M. Feldmann, F. M. Brennan, and R. N. Maini, “Role of cytokines in rheumatoid arthritis,” Annual Review of Immunology, vol. 14, pp. 397–440, 1996. View at Publisher · View at Google Scholar · View at Scopus
  3. C. Tanasescu, C. Jurcut, R. Jurcut, and C. Ginghina, “Vascular disease in rheumatoid arthritis: from subclinical lesions to cardiovascular risk,” European Journal of Internal Medicine, vol. 20, no. 4, pp. 348–354, 2009. View at Publisher · View at Google Scholar · View at Scopus
  4. D. E. Furst, R. W. Ulrich, and C. Varkey-Altamirano, “Nonsteroidal anti-inflammatory drugs, disease modifying antirheumatic drugs, nonopiod analgesics & drugs used in gout,” in Basic and Clinical Pharmacology, B. G. Katzung, S. B. Masters, and A. J. Trevor, Eds., pp. 621–642, McGraw Hill, New York, NY, USA, 11th edition, 2009.
  5. G. A. FitzGerald, “Coxibs and cardiovascular disease,” New England Journal of Medicine, vol. 351, no. 17, pp. 1709–1711, 2004. View at Publisher · View at Google Scholar · View at Scopus
  6. E. S. L. Chan and B. N. Cronstein, “Methotrexatehow does it really work?” Nature Reviews Rheumatology, vol. 6, no. 3, pp. 175–178, 2010. View at Publisher · View at Google Scholar · View at Scopus
  7. J. Castellsague, C. N. Holick, C. C. Hoffman, V. Gimeno, M. R. Stang, and S. Perez-Gutthann, “Risk of upper gastrointestinal complications associated with cyclooxygenase-2 selective and nonselective nonsteroidal antiinflammatory drugs,” Pharmacotherapy, vol. 29, no. 12, pp. 1397–1407, 2009. View at Publisher · View at Google Scholar · View at Scopus
  8. S. X. Sun, K. Y. Lee, C. T. Bertram, and J. L. Goldstein, “Withdrawal of COX-2 selective inhibitors rofecoxib and valdecoxib: impact on NSAID and gastroprotective drug prescribing and utilization,” Current Medical Research and Opinion, vol. 23, no. 8, pp. 1859–1866, 2007. View at Publisher · View at Google Scholar · View at Scopus
  9. E. S. L. Chan, S. N. Oliver, and B. N. Cronstein, “Immunomodulating pharmaceuticals,” in Clinical Immunology: Principles and Practice, R. R. Rich, T. A. Fleisher, W. T. Shearer, H. W. Schroeder, A. J. Frew, and C. M. Weyand, Eds., pp. 90-1–90-9, Mosby Elsevier, Philadelphia, Pa, USA, 3rd edition, 2008.
  10. S. L. Westlake, A. N. Colebatch, J. Baird et al., “The effect of methotrexate on cardiovascular disease in patients with rheumatoid arthritis: a systematic literature review,” Rheumatology, vol. 49, no. 2, pp. 295–307, 2009. View at Publisher · View at Google Scholar · View at Scopus
  11. A. Reiss, H. Zhang, S. Edelman, et al., “Unraveling coxib atherogenicity: adenosine A2A receptor agonists reverse disruption of cholesterol efflux induced by cyclooxygenase (COX)-2 inhibition,” Inflammation Research, vol. 55, pp. S117–S118, 2006.
  12. A. B. Reiss, F. Anwar, E. S. L. Chan, and K. Anwar, “Disruption of cholesterol efflux by coxib medications and inflammatory processes: link to increased cardiovascular risk,” Journal of Investigative Medicine, vol. 57, no. 6, pp. 695–702, 2009. View at Publisher · View at Google Scholar · View at Scopus
  13. A. B. Reiss, S. E. Carsons, K. Anwar et al., “Atheroprotective effects of methotrexate on reverse cholesterol transport proteins and foam cell transformation in human THP-1 monocyte/macrophages,” Arthritis and Rheumatism, vol. 58, no. 12, pp. 3675–3683, 2008. View at Publisher · View at Google Scholar · View at Scopus
  14. E. S. L. Chan, H. Zhang, P. Fernandez et al., “Effect of cyclooxygenase inhibition on cholesterol efflux proteins and atheromatous foam cell transformation in THP-1 human macrophages: a possible mechanism for increased cardiovascular risk,” Arthritis Research and Therapy, vol. 9, Article ID R4, 2007. View at Publisher · View at Google Scholar · View at Scopus
  15. V. Ralevic and G. Burnstock, “Receptors for purines and pyrimidines,” Pharmacological Reviews, vol. 50, no. 3, pp. 413–492, 1998. View at Scopus
  16. M. E. Olah and G. L. Stiles, “The role of receptor structure in determining adenosine receptor activity,” Pharmacology and Therapeutics, vol. 85, no. 2, pp. 55–75, 2000. View at Publisher · View at Google Scholar · View at Scopus
  17. M. C. Montesinos, A. Desai, and B. N. Cronstein, “Suppression of inflammation by low-dose methotrexate is mediated by adenosine A receptor but not A receptor activation in thioglycollate-induced peritonitis,” Arthritis Research and Therapy, vol. 8, no. 2, Article ID R53, 2006. View at Publisher · View at Google Scholar · View at Scopus
  18. J. A. McPherson, K. G. Barringhaus, G. G. Bishop et al., “Adenosine A receptor stimulation reduces inflammation and neointimal growth in a murine carotid ligation model,” Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 21, no. 5, pp. 791–796, 2001. View at Scopus
  19. P. A. Borea, S. Gessi, S. Bar-Yehuda, and P. Fishman, “A adenosine receptor: pharmacology and role in disease,” Handbook of Experimental Pharmacology, vol. 193, pp. 297–327, 2009. View at Publisher · View at Google Scholar · View at Scopus
  20. S. Nakav, C. Chaimovitz, Y. Sufaro et al., “Anti-inflammatory preconditioning by agonists of adenosine A1 receptor,” PLoS One, vol. 3, no. 5, Article ID e2107, 2008. View at Publisher · View at Google Scholar · View at Scopus
  21. R. Ross, “Atherosclerosis—an inflammatory disease,” New England Journal of Medicine, vol. 340, no. 2, pp. 115–126, 1999. View at Publisher · View at Google Scholar
  22. P. Libby, “Changing concepts of atherogenesis,” Journal of Internal Medicine, vol. 247, no. 3, pp. 349–358, 2000. View at Publisher · View at Google Scholar · View at Scopus
  23. A. Von Eckardstein, J. R. Nofer, and G. Assmann, “High density lipoproteins and arteriosclerosis role of cholesterol efflux and reverse cholesterol transport,” Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 21, no. 1, pp. 13–27, 2001. View at Scopus
  24. H. S. Kruth, “Macrophage foam cells and atherosclerosis,” Frontiers in Bioscience, vol. 6, pp. D429–D455, 2001. View at Scopus
  25. R. Ohashi, H. Mu, X. Wang, Q. Yao, and C. Chen, “Reverse cholesterol transport and cholesterol efflux in atherosclerosis,” Monthly Journal of the Association of Physicians, vol. 98, no. 12, pp. 845–856, 2005. View at Publisher · View at Google Scholar · View at Scopus
  26. J. F. Oram and R. M. Lawn, “ABCA1: the gatekeeper for eliminating excess tissue cholesterol,” Journal of Lipid Research, vol. 42, no. 8, pp. 1173–1179, 2001. View at Scopus
  27. N. Terasaka, N. Wang, L. Yvan-Charvet, and A. R. Tall, “High-density lipoprotein protects macrophages from oxidized low-density lipoprotein-induced apoptosis by promoting efflux of 7-ketocholesterol via ABCG1,” Proceedings of the National Academy of Sciences of the United States of America, vol. 104, no. 38, pp. 15093–15098, 2007. View at Publisher · View at Google Scholar · View at Scopus
  28. A. Babiker, O. Andersson, E. Lund et al., “Elimination of cholesterol in macrophages and endothelial cells by the sterol 27-hydroxylase mechanism. Comparison with high density lipoprotein- mediated reverse cholesterol transport,” Journal of Biological Chemistry, vol. 272, no. 42, pp. 26253–26261, 1997. View at Publisher · View at Google Scholar · View at Scopus
  29. X. Wang and D. J. Rader, “Molecular regulation of macrophage reverse cholesterol transport,” Current Opinion in Cardiology, vol. 22, no. 4, pp. 368–372, 2007. View at Publisher · View at Google Scholar · View at Scopus
  30. G. D. Kolovou, D. P. Mikhailidis, K. K. Anagnostopoulou, S. S. Daskalopoulou, and D. V. Cokkinos, “Tangier disease four decades of research: a reflection of the importance of HDL,” Current Medicinal Chemistry, vol. 13, no. 7, pp. 771–782, 2006. View at Publisher · View at Google Scholar · View at Scopus
  31. I. Iatan, K. Alrasadi, I. Ruel, K. Alwaili, and J. Genest, “Effect of ABCA1 mutations on risk for myocardial infarction,” Current Atherosclerosis Reports, vol. 10, no. 5, pp. 413–426, 2008. View at Publisher · View at Google Scholar · View at Scopus
  32. C. Albrecht, S. Soumian, J. S. Amey et al., “ABCA1 expression in carotid atherosclerotic plaques,” Stroke, vol. 35, no. 12, pp. 2801–2806, 2004. View at Publisher · View at Google Scholar · View at Scopus
  33. M. Lee-Rueckert, J. Lappalainen, H. Leinonen, T. Pihlajamaa, M. Jauhiainen, and P. T. Kovanen, “Acidic extracellular environments strongly impair ABCA1-mediated cholesterol efflux from human macrophage foam cells,” Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 30, no. 9, pp. 1766–1772, 2010. View at Publisher · View at Google Scholar
  34. M. Naghavi, R. John, S. Naguib et al., “pH heterogeneity of human and rabbit atherosclerotic plaques; a new insight into detection of vulnerable plaque,” Atherosclerosis, vol. 164, no. 1, pp. 27–35, 2002. View at Publisher · View at Google Scholar · View at Scopus
  35. A. B. Reiss and A. D. Glass, “Atherosclerosis: immune and inflammatory aspects,” Journal of Investigative Medicine, vol. 54, no. 3, pp. 123–131, 2006. View at Publisher · View at Google Scholar · View at Scopus
  36. V. M. Olkkonen and M. Lehto, “Oxysterols and oxysterol binding proteins: role in lipid metabolism and atherosclerosis,” Annals of Medicine, vol. 36, no. 8, pp. 562–572, 2004. View at Publisher · View at Google Scholar · View at Scopus
  37. I. Björkhem and U. Diczfalusy, “Oxysterols: friends, foes, or just fellow passengers?” Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 22, no. 5, pp. 734–742, 2002. View at Publisher · View at Google Scholar · View at Scopus
  38. I. Bjorkhem, O. Andersson, U. Diczfalusy et al., “Atherosclerosis and sterol 27-hydroxylase: evidence for a role of this enzyme in elimination of cholesterol from human macrophages,” Proceedings of the National Academy of Sciences of the United States of America, vol. 91, no. 18, pp. 8592–8596, 1994. View at Scopus
  39. A. Babiker, S. Dzeletovic, B. Wiklund et al., “Patients with atherosclerosis may have increased circulating levels of 27-hydroxycholesterol and cholestenoic acid,” Scandinavian Journal of Clinical and Laboratory Investigation, vol. 65, no. 5, pp. 365–376, 2005. View at Publisher · View at Google Scholar · View at Scopus
  40. X. Fu, J. G. Menke, Y. Chen et al., “27-hydroxycholesterol is an endogenous ligand for liver X receptor in cholesterol-loaded cells,” Journal of Biological Chemistry, vol. 276, no. 42, pp. 38378–38387, 2001. View at Publisher · View at Google Scholar · View at Scopus
  41. S. Murthy, E. Born, S. N. Mathur, and F. J. Field, “LXR/RXR activation enhances basolateral efflux of cholesterol in CaCo-2 cells,” Journal of Lipid Research, vol. 43, no. 7, pp. 1054–1064, 2002. View at Publisher · View at Google Scholar · View at Scopus
  42. P. A. Edwards, M. A. Kennedy, and P. A. Mak, “LXRs; Oxysterol-activated nuclear receptors that regulate genes controlling lipid homeostasis,” Vascular Pharmacology, vol. 38, no. 4, pp. 249–256, 2002. View at Publisher · View at Google Scholar · View at Scopus
  43. A. B. Reiss, “Effects of inflammation on cholesterol metabolism: impact on systemic lupus erythematosus,” Current Rheumatology Reports, vol. 11, no. 4, pp. 255–260, 2009. View at Publisher · View at Google Scholar · View at Scopus
  44. J. George, D. Harats, B. Gilburd, Y. Levy, P. Langevitz, and Y. Shoenfeld, “Atherosclerosis-related markers in systemic lupus erythematosus patients: the role of humoral immunity in enhanced atherogenesis,” Lupus, vol. 8, no. 3, pp. 220–226, 1999. View at Scopus
  45. G. Virella and M. F. Lopes-Virella, “Atherogenesis and the humoral immune response to modified lipoproteins,” Atherosclerosis, vol. 200, no. 2, pp. 239–246, 2008. View at Publisher · View at Google Scholar · View at Scopus
  46. A. B. Reiss, M. M. Rahman, E. S. L. Chan, M. C. Montesinos, N. W. Awadallah, and B. N. Cronstein, “Adenosine A receptor occupancy stimulates expression of proteins involved in reverse cholesterol transport and inhibits foam cell formation in macrophages,” Journal of Leukocyte Biology, vol. 76, no. 3, pp. 727–734, 2004. View at Publisher · View at Google Scholar · View at Scopus
  47. A. B. Reiss, N. W. Awadallah, S. Malhotra et al., “Immune complexes and IFN-γ decrease cholesterol 27-hydroxylase in human arterial endothelium and macrophages,” Journal of Lipid Research, vol. 42, no. 11, pp. 1913–1922, 2001. View at Scopus
  48. X. R. Hao, D. L. Cao, Y. W. Hu et al., “IFN-γ down-regulates ABCA1 expression by inhibiting LXRα in a JAK/STAT signaling pathway-dependent manner,” Atherosclerosis, vol. 203, no. 2, pp. 417–428, 2009. View at Publisher · View at Google Scholar · View at Scopus
  49. K. E. Barnholt, R. S. Kota, H. H. Aung, and J. C. Rutledge, “Adenosine blocks IFN-γ-induced phosphorylation of STAT1 on serine 727 to reduce macrophage activation,” Journal of Immunology, vol. 183, no. 10, pp. 6767–6777, 2009. View at Publisher · View at Google Scholar · View at Scopus
  50. J. E. McLaren and D. P. Ramji, “Interferon gamma: a master regulator of atherosclerosis,” Cytokine and Growth Factor Reviews, vol. 20, no. 2, pp. 125–135, 2009. View at Publisher · View at Google Scholar · View at Scopus
  51. J. S. Nair, C. J. DaFonseca, A. Tjernberg et al., “Requirement of Ca2+ and CaMKII for Stat1 Ser-727 phosphorylation in response to IFN-γ,” Proceedings of the National Academy of Sciences of the United States of America, vol. 99, no. 9, pp. 5971–5976, 2002. View at Publisher · View at Google Scholar · View at Scopus
  52. R. B. M. Landewé, B. E. E. M. Van Den Borne, F. C. Breedveld, and B. A. C. Dijkmans, “Methotrexate effects in patients with rheumatoid arthritis with cardiovascular comorbidity,” Lancet, vol. 355, no. 9215, pp. 1616–1617, 2000. View at Scopus
  53. J. Lynge, G. Schulte, N. Nordsborg, B. B. Fredholm, and Y. Hellsten, “Adenosine A receptors modulate cAMP levels and induce CREB but not ERK1/2 and p38 phosphorylation in rat skeletal muscle cells,” Biochemical and Biophysical Research Communications, vol. 307, no. 1, pp. 180–187, 2003. View at Publisher · View at Google Scholar · View at Scopus
  54. T. C. Bingham, E. A. Fisher, S. Parathath, A. B. Reiss, E. S. Chan, and B. N. Cronstein, “A2A adenosine receptor stimulation decreases foam cell formation by enhancing ABCA1-dependent cholesterol efflux,” Journal of Leukocyte Biology, vol. 87, no. 4, pp. 683–690, 2010. View at Publisher · View at Google Scholar · View at Scopus
  55. J. L. Bos, “Epac: a new cAMP target and new avenues in cAMP research,” Nature Reviews Molecular Cell Biology, vol. 4, no. 9, pp. 733–738, 2003. View at Publisher · View at Google Scholar · View at Scopus
  56. L. Martin, S. C. Pingle, D. M. Hallam, L. P. Rybak, and V. Ramkumar, “Activation of the adenosine A receptor in RAW 264.7 cells inhibits lipopolysaccharide-stimulated tumor necrosis factor-α release by reducing calcium-dependent activation of nuclear factor-κB and extracellular signal-regulated kinase 1/2,” Journal of Pharmacology and Experimental Therapeutics, vol. 316, no. 1, pp. 71–78, 2006. View at Publisher · View at Google Scholar · View at Scopus
  57. P. M. Ridker, “Testing the inflammatory hypothesis of atherothrombosis: scientific rationale for the cardiovascular inflammation reduction trial (CIRT),” Journal of Thrombosis and Haemostasis, vol. 7, no. 1, pp. 332–339, 2009. View at Publisher · View at Google Scholar · View at Scopus