Table of Contents Author Guidelines Submit a Manuscript
Experimental Diabetes Research
Volume 2012, Article ID 231502, 9 pages
http://dx.doi.org/10.1155/2012/231502
Clinical Study

Low Levels of Serum Paraoxonase Activities are Characteristic of Metabolic Syndrome and May Influence the Metabolic-Syndrome-Related Risk of Coronary Artery Disease

1Department of Medicine, University of Verona, Policlinico G.B. Rossi, 37134 Verona, Italy
2Department of Life and Reproduction Sciences, University of Verona, 37134 Verona, Italy

Received 30 June 2011; Accepted 20 July 2011

Academic Editor: Jun Ren

Copyright © 2012 Nicola Martinelli 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. K. G. Alberti, R. H. Eckel, S. M. Grundy et al., “Harmonizing the metabolic syndrome: a joint interim statement of the International Diabetes Federation Task Force on Epidemiology and Prevention; National Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; and International Association for the Study of Obesity,” Circulation, vol. 120, no. 16, pp. 1640–1645, 2009. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  2. S. M. Grundy, “Metabolic syndrome: a multiplex cardiovascular risk factor,” Journal of Clinical Endocrinology and Metabolism, vol. 92, no. 2, pp. 399–404, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  3. N. Sattar, “The metabolic syndrome: should current criteria influence clinical practice?” Current Opinion in Lipidology, vol. 17, no. 4, pp. 404–411, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  4. A. Whaley-Connell, P. A. McCullough, and J. R. Sowers, “The role of oxidative stress in the metabolic syndrome,” Reviews in Cardiovascular Medicine, vol. 12, pp. 21–29, 2011. View at Google Scholar
  5. P. Libby, “Inflammation in atherosclerosis,” Nature, vol. 420, no. 6917, pp. 868–874, 2002. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  6. S. Parthasarathy, J. Barnett, and L. G. Fong, “High-density lipoprotein inhibits the oxidative modification of low-density lipoprotein,” Biochimica et Biophysica Acta, vol. 1044, no. 2, pp. 275–283, 1990. View at Publisher · View at Google Scholar · View at Scopus
  7. M. Navab, G. M. Ananthramaiah, S. T. Reddy et al., “The oxidation hypothesis of atherogenesis: the role of oxidized phospholipids and HDL,” Journal of Lipid Research, vol. 45, no. 6, pp. 993–1007, 2004. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  8. M. Navab, S. Y. Hama, G. M. Anantharamaiah et al., “Normal high density lipoprotein inhibits three steps in the formation of mildly oxidized low density lipoprotein: steps 2 and 3,” Journal of Lipid Research, vol. 41, no. 9, pp. 1495–1508, 2000. View at Google Scholar · View at Scopus
  9. M. Navab, S. T. Reddy, B. J. Van Lenten, G. M. Anantharamaiah, and A. M. Fogelman, “The role of dysfunctional HDL in atherosclerosis,” Journal of Lipid Research, vol. 50, pp. S145–S149, 2009. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  10. G. W. Cockerill, K. A. Rye, J. R. Gamble, M. A. Vadas, and P. J. Barter, “High-density lipoproteins inhibit cytokine-induced expression of endothelial cell adhesion molecules,” Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 15, no. 11, pp. 1987–1994, 1995. View at Google Scholar · View at Scopus
  11. L. Calabresi, M. Gomaraschi, B. Villa, L. Omoboni, C. Dmitrieff, and G. Franceschini, “Elevated soluble cellular adhesion molecules in subjects with low HDL-cholesterol,” Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 22, no. 4, pp. 656–661, 2002. View at Publisher · View at Google Scholar · View at Scopus
  12. G. W. Cockerill, T. Y. Huehns, A. Weerasinghe et al., “Elevation of plasma high-density lipoprotein concentration reduces interleukin-1-induced expression of E selectin in an in vivo model of acute inflammation,” Circulation, vol. 103, no. 1, pp. 108–112, 2001. View at Google Scholar · View at Scopus
  13. R. W. James, “A long and winding road: defining the biological role and clinical importance of paraoxonases,” Clinical Chemistry and Laboratory Medicine, vol. 44, no. 9, pp. 1052–1059, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  14. J. Camps, J. Marsillach, and J. Joven, “The paraoxonases: role in human diseases and methodological difficulties in measurement,” Critical Reviews in Clinical Laboratory Sciences, vol. 46, no. 2, pp. 83–106, 2009. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  15. M. Harel, A. Aharoni, L. Gaidukov et al., “Structure and evolution of the serum paraoxonase family of detoxifying and anti-atherosclerotic enzymes,” Nature Structural and Molecular Biology, vol. 11, no. 5, pp. 412–419, 2004. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  16. O. Khersonsky and D. S. Tawfik, “Structure-reactivity studies of serum paraoxonase PON1 suggest that its native activity is lactonase,” Biochemistry, vol. 44, no. 16, pp. 6371–6382, 2005. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  17. D. I. Draganov, J. F. Teiber, A. Speelman, Y. Osawa, R. Sunahara, and B. N. La Du, “Human paraoxonases (PON1, PON2, and PON3) are lactonases with overlapping and distinct substrate specificities,” Journal of Lipid Research, vol. 46, no. 6, pp. 1239–1247, 2005. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  18. M. Sentí, M. Tomás, M. Fitó et al., “Antioxidant paraoxonase 1 activity in the metabolic syndrome,” Journal of Clinical Endocrinology and Metabolism, vol. 88, no. 11, pp. 5422–5426, 2003. View at Publisher · View at Google Scholar · View at Scopus
  19. M. C. Blatter Garin, B. Kalix, A. Morabia, and R. W. James, “Small, dense lipoprotein particles and reduced paraoxonase-1 in patients with the metabolic syndrome,” Journal of Clinical Endocrinology & Metabolism, vol. 90, pp. 2264–2269, 2005. View at Google Scholar
  20. L. Gaidukov and D. S. Tawfik, “The development of human sera tests for HDL-bound serum PON1 and its lipolactonase activity,” Journal of Lipid Research, vol. 48, no. 7, pp. 1637–1646, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  21. N. Martinelli, D. Girelli, O. Olivieri et al., “Novel serum paraoxonase activity assays are associated with coronary artery disease,” Clinical Chemistry and Laboratory Medicine, vol. 47, no. 4, pp. 432–440, 2009. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  22. N. Martinelli, D. Girelli, B. Lunghi et al., “Polymorphisms at LDLR locus may be associated with coronary artery disease through modulation of coagulation factor VIII activity and independently from lipid profile,” Blood, vol. 116, no. 25, pp. 5688–5697, 2010. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  23. “Expert panel on detection, evaluation, and treatment of high blood cholesterol in adults executive summary of the third report of the National Cholesterol Education Program (NCEP) expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (adult treatment panel III),” Journal of the American Medical Association, vol. 285, pp. 2486–2497, 2001.
  24. S. Cheng, M. A. Grow, C. Pallaud et al., “A multilocus genotyping assay for candidate markers of cardiovascular disease risk,” Genome Research, vol. 9, no. 10, pp. 936–949, 1999. View at Publisher · View at Google Scholar · View at Scopus
  25. M. I. Mackness, S. Arrol, and P. N. Durrington, “Paraoxonase prevents accumulation of lipoperoxides in low-density lipoprotein,” FEBS Letters, vol. 286, no. 1-2, pp. 152–154, 1991. View at Publisher · View at Google Scholar · View at Scopus
  26. D. M. Shih and A. J. Lusis, “The roles of PON1 and PON2 in cardiovascular disease and innate immunity,” Current Opinion in Lipidology, vol. 20, no. 4, pp. 288–292, 2009. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  27. H. J. Bouman, E. Schömig, J. W. van Werkum et al., “Paraoxonase-1 is a major determinant of clopidogrel efficacy,” Nature Medicine, vol. 17, pp. 110–116, 2010. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  28. M. I. Mackness, S. Arrol, C. Abbott, and P. N. Durrington, “Protection of low-density lipoprotein against oxidative modification by high-density lipoprotein associated paraoxonase,” Atherosclerosis, vol. 104, no. 1-2, pp. 129–135, 1993. View at Google Scholar · View at Scopus
  29. M. Aviram, M. Rosenblat, C. L. Bisgaier, R. S. Newton, S. L. Primo-Parmo, and B. N. La Du, “Paraoxonase inhibits high-density lipoprotein oxidation and preserves its functions. A possible peroxidative role for paraoxonase,” Journal of Clinical Investigation, vol. 101, no. 8, pp. 1581–1590, 1998. View at Google Scholar · View at Scopus
  30. M. Aviram, M. Rosenblat, S. Billecke et al., “Human serum paraoxonase (PON 1) is inactivated by oxidized low density lipoprotein and preserved by antioxidants,” Free Radical Biology and Medicine, vol. 26, no. 7-8, pp. 892–904, 1999. View at Publisher · View at Google Scholar · View at Scopus
  31. S. E. Nissen, J. C. Tardif, S. J. Nicholls et al., “Effect of torcetrapib on the progression of coronary atherosclerosis,” The New England Journal of Medicine, vol. 356, no. 13, pp. 1304–1316, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  32. P. J. Barter, M. Caulfield, M. Eriksson et al., “Effects of torcetrapib in patients at high risk for coronary events,” The New England Journal of Medicine, vol. 357, no. 21, pp. 2109–2122, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  33. T. Joy and R. A. Hegele, “Is raising HDL a futile strategy for atheroprotection?” Nature Reviews Drug Discovery, vol. 7, no. 2, pp. 143–155, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  34. A. von Eckardstein, “Implications of torcetrapib failure for the future of HDL therapy: is HDL-cholesterol the right target?” Expert Review of Cardiovascular Therapy, vol. 8, no. 3, pp. 345–358, 2010. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  35. B. Mackness, R. Quarck, W. Verreth, M. Mackness, and P. Holvoet, “Human paraoxonase-1 overexpression inhibits atherosclerosis in a mouse model of metabolic syndrome,” Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 26, no. 7, pp. 1545–1550, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  36. C. Besler, K. Heinrich, L. Rohrer et al., “Mechanisms underlying adverse effects of HDL on eNOS-activating pathways in patients with coronary artery disease,” Journal of Clinical Investigation, vol. 121, pp. 2693–2708, 2011. View at Google Scholar
  37. C. Mineo and P. W. Shaul, “PON-dering differences in HDL function in coronary artery disease,” Journal of Clinical Investigation, vol. 121, pp. 2545–2548, 2011. View at Google Scholar