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Paraoxonase-1 activity as a marker of atherosclerosis is not associated with low bone mineral density in healthy postmenopausal women

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Abstract

The aging process is associated with an increasing prevalence of osteoporosis and atherosclerosis, but it is uncertain if these two conditions are interrelated. Serum paraoxonase-1 (PON1) is a high-density lipoprotein (HDL) associated enzyme that has been implicated in the pathogenesis of atherosclerosis. Our aims of the study were to investigate (1) serum paraoxonase and arylesterase activities and, lipid hydroperoxide (LOOH) levels in healthy postmenopausal women and (2) whether there were any associations between these enzyme activities and bone mineral density (BMD). A total of 97 generally healthy postmenopausal women were enrolled in the study. BMD was measured at lumbar spine (LS) and femoral neck (FN) with dual energy X-ray absorptiometry. Serum paraoxonase and arylesterase activities were measured spectrophotometrically. LOOH levels were measured by iodometric assay. In this population, 50 (51%) women had BMD T scores < −2.5 at the LS and/or FN defined as osteoporosis and 47 (49%) of them had normal BMDs. Serum paraoxonase, arylesterase, and LOOH activities were not significantly different between osteoporotic and nonosteoporotic postmenopausal women. There were also no correlations between paraoxonase, arylesterase, LOOH activities, and LS BMD and FN BMD. We conclude that there may be not good evidence to support a direct relationship between osteoporosis and atherosclerosis in these subjects. However, prospective studies with larger groups are needed to investigate this issue further.

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References

  1. Ahmed Z, Ravandi A, Maguire GF, Emili A, Draganov D, La Du BN, Kuksis A, Connelly PW (2001) Apolipoprotein A-I promotes the formation of phosphatidylcholine core aldehydes that are hydrolyzed by paraoxonase (PON−1) during high density lipoprotein oxidation with a peroxynitrite donor. J Biol Chem 276:24473–24481

    Article  PubMed  CAS  Google Scholar 

  2. Ahmed Z, Ravandi A, Maguire GF, Emili A, Draganov D, La Du BN, Kuksis A, Connelly PW (2002) Multiple substrates for paraoxonase-1 during oxidation of phosphatidylcholine by peroxynitrite. Biochem Biophys Res Commun 290:391–396

    Article  PubMed  CAS  Google Scholar 

  3. Anderson JJ (2002) Oversupplementation of vitamin A and osteoporotic fractures in the elderly: to supplement or not to supplement with vitamin A. J Bone Miner Res 17:1359–1362

    Article  PubMed  Google Scholar 

  4. Aoyagi K, Ross PD, Orloff J, Davis JW, Katagiri H, Wasnich RD (2001) Low bone density is not associated with aortic calcification. Calcif Tissue Int 69:20–24

    Article  PubMed  CAS  Google Scholar 

  5. Aslan M, Kosecik M, Horoz M, Selek S, Celik H, Erel O (2006) Assessment of paraoxonase and arylesterase activities in patients with iron deficiency anemia. Atherosclerosis [Epub ahead of print]

  6. Aviram M, Rosenblat M, Bisgaier CL, Newton RS, Primo-Parmo SL, La Du BN (1998) Paraoxonase inhibits high density lipoprotein (HDL) oxidation and preserves its functions: a possible peroxidative role for paraoxonase. J Clin Invest 101:1581–1590

    PubMed  CAS  Google Scholar 

  7. Aviram M, Billecke S, Sorenson R, Bisgaier C, Newton R, Rosenblat M, Erogul J, Hsu C, Dunlop C, La Du B (1998) Paraoxonase active site required for protection against LDL oxidation involves its free sulfhydryl group and is different from that required for its arylesterase/paraoxonase activities: selective action of human paraoxonase allozymes Q and R. Arterioscler Thromb Vasc Biol 18:1617–1624

    PubMed  CAS  Google Scholar 

  8. Aviram M, Hardak E, Vaya J, Mahmood S, Milo S, Hoffman A, Billicke S, Draganov D, Rosenblat M (2000) Human serum paraoxonases (PON1) Q and R selectively decrease lipid peroxides in human coronary and carotid atherosclerotic lesions: PON1 esterase and peroxidase-like activities. Circulation 101:2510–2517

    PubMed  CAS  Google Scholar 

  9. Aviram M, Rosenblat M (2004) Paraoxonases 1, 2, and 3, oxidative stress, and macrophage foam cell formation during atherosclerosis development. Free Radic Biol Med 37:1304–1316

    Article  PubMed  CAS  Google Scholar 

  10. Ayub A, Mackness MI, Arrol S, Mackness B, Patel J, Durrington PN (1999) Serum paraoxonase after myocardial infarction. Arterioscler Thromb Vasc Biol 19:330–335

    PubMed  CAS  Google Scholar 

  11. Barengolts EI, Berman M, Kukreja SC, Kouznetsova T, Lin C, Chomka EV (1998) Osteoporosis and coronary atherosclerosis in asymptomatic postmenopausal women. Calcif Tissue Int 62:209–213

    Article  PubMed  CAS  Google Scholar 

  12. Basu S, Michaelsson K, Olofsson H, Johansson S, Melhus H (2001) Association between oxidative stress and bone mineral density. Biochem Biophys Res Commun 288:275–279

    Article  PubMed  CAS  Google Scholar 

  13. Chung YS, Lee MD, Lee SK, Kim HM, Fitzpatrick LA (2000) HMG-CoA reductase inhibitors increase BMD in type 2 diabetes mellitus patients. J Clin Endocrinol Metab 85:1137–1142

    Article  PubMed  CAS  Google Scholar 

  14. Durrington PN, Mackness B, Mackness MI (2001) Paraoxonase and atherosclerosis. Arterioscler Thromb Vasc Biol 21:473–480

    PubMed  CAS  Google Scholar 

  15. Frye MA, Melton LJ III, Bryant SC, Fitzpatrick LA, Wahner HW, Schwartz RS, Riggs BL (1992) Osteoporosis and calcification of the aorta. Bone Miner 19:185–194

    Article  PubMed  CAS  Google Scholar 

  16. Fuhrman B, Volkova N, Aviram M (2002) Oxidative stress increases the expression of the CD36 scavenger receptor and the cellular uptake of oxidized low-density lipoprotein in macrophages from atherosclerotic mice: protective role of antioxidants and of paraoxonase. Atherosclerosis 161:307–316

    Article  PubMed  CAS  Google Scholar 

  17. Girotti AW (1998) Lipid hydroperoxide generation, turnover, and effector action in biological systems. J Lipid Res 39:1529–1542

    PubMed  CAS  Google Scholar 

  18. Gorog P, Kotak DC, Kovacs IB (1991) Simple and specific test for measuring lipid peroxides in plasma. J Clin Pathol 44:765–767

    PubMed  CAS  Google Scholar 

  19. Gorog DA, Ahmed N, Davies GJ (2002) Elevated plasma lipid peroxide levels in angina pectoris and myocardial infarction. Cardiovasc Pathol 11:153–157

    Article  PubMed  CAS  Google Scholar 

  20. Hak AE, Pols HAP, van Hemert AM, Hofman A, Witteman JCM (2000) Progression of aortic calcification is associated with metacarpal bone loss during menopause: a population-based longitudinal study. Arterioscler Thromb Vasc Biol 20:1926–1931

    PubMed  CAS  Google Scholar 

  21. Hall SL, Greendale GA (1998) The relation of dietary Vitamin C intake to bone mineral density: results from the PEPI study. Calcif Tissue Int 63:183–189

    Article  PubMed  CAS  Google Scholar 

  22. Hirose K, Tomiyama H, Okazaki R, Arai T, Koji Y, Zaydun G, Hori S, Yamashina A (2003) Increased pulse wave velocity associated with reduced calcaneal quantitative osteo-sono index: possible relationship between atherosclerosis and osteopenia. J Clin Endocrinol Metab 88:2573–2578

    Article  PubMed  CAS  Google Scholar 

  23. Isik A, Koca SS, Ustundag B, Celik H, Yildirim A (2006) Paraoxonase and arylesterase levels in rheumatoid arthritis. Clin Rheumatol [Epub ahead of print]

  24. Jarvik GP, Rozek LS, Brophy VH, Hatsukami TS, Richter RJ, Schellenberg GD, Furlong CE (2000) Paraoxonase (PON1) phenotype is a better predictor of vascular disease than is PON1(192) or PON1(55) genotype. Arterioscler Thromb Vasc Biol 20:2441–2447

    PubMed  CAS  Google Scholar 

  25. Kiel DP, Kauppila LI, Cupples LA, Hannan MT, O’Donnell CJ, Wilson PWF (2001) Bone loss and the progression of abdominal aortic calcification over a 25 year period: the Framingham Heart Study. Calcif Tissue Int 68:271–276

    Article  PubMed  CAS  Google Scholar 

  26. Leitinger N (2003) Cholesteryl ester oxidation products in atherosclerosis. Mol Aspects Med 24:239–250

    Article  PubMed  CAS  Google Scholar 

  27. Luegmayr E, Glantschnig H, Wesolowski GA, Gentile MA, Fisher JE, Rodan GA, Reszka AA (2004) Osteoclast formation, survival and morphology are highly dependent on exogenous cholesterol/lipoproteins. Cell Death Differ 11:108–118

    Article  CAS  Google Scholar 

  28. Mackness MI, Arrol S, Durrington PN (1991) Paraoxonase prevents accumulation of lipoperoxides in low-density lipoprotein. FEBS Lett 286:152–154

    Article  PubMed  CAS  Google Scholar 

  29. Mackness MI, Arrol S, Abbott C, Durrington PN (1993) Protection of low-density lipoprotein against oxidative modification by high-density lipoprotein associated paraoxonase. Atherosclerosis 104:129–135

    Article  PubMed  CAS  Google Scholar 

  30. Mackness B, Durrington PN, Abuashia B, Boulton AJ, Mackness MI (2000) Low paraoxonase activity in type II diabetes mellitus complicated by retinopathy. Clin Sci (Lond) 98:355–363

    Article  CAS  Google Scholar 

  31. Mackness B, Durrington P, McElduff P, Yarnell J, Azam N, Watt M, Mackness M (2003) Low paraoxonase activity predicts coronary events in the Caerphilly prospective study. Circulation 107:2775–2779

    Article  PubMed  CAS  Google Scholar 

  32. Maggio D, Barabani M, Pierandrei M, Polidori MC, Catani M, Mecocci P, Senin U, Pacifici R, Cherubini A (2003) Marked decrease in plasma antioxidants in aged osteoporotic women: results of a cross-sectional study. J Clin Endocrinol Metab 88:1523–1527

    Article  PubMed  CAS  Google Scholar 

  33. Magnus JH, Broussard DL (2005) Relationship between bone mineral density and myocardial infarction in US adults. Osteoporos Int 16:2053–2062

    Article  PubMed  Google Scholar 

  34. McElveen J, Mackness MI, Colley CM, Peard T, Warner S, Walker CH (1986) Distribution of paraoxon hydrolysing activity in the serum of patients after myocardial infarction. Clin Chem 32:671–673

    PubMed  CAS  Google Scholar 

  35. Navab M, Berliner JA, Watson AD, Hama SY, Territo MC, Lusis AJ, Shih DM, Van Lenten BJ, Frank JS, Demer LL, Edwards PA, Fogelman AM (1996) The Yin and Yang of oxidation in the development of the fatty streak. A review based on the 1994 George Lyman Duff Memorial Lecture. Arterioscler Thromb Vasc Biol 16:831–842

    PubMed  CAS  Google Scholar 

  36. Oda MN, Bielicki JK, Ho TT, Berger T, Rubin EM, Forte TM (2002) Paraoxonase 1 overexpression in mice and its effect on high-density lipoproteins. Biochem Biophys Res Commun 290:921–927

    Article  PubMed  CAS  Google Scholar 

  37. Parhami F, Tintut Y, Beamer WG, Gharavi N, Goodman W, Demer LL (2001) Atherogenic high-fat diet reduces bone mineralization in mice. J Bone Miner Res 16:182–188

    Article  PubMed  CAS  Google Scholar 

  38. Pennisi P, Signorelli SS, Riccobene S, Celotta G, Di Pino L, La Malfa T, Fiore CE (2004) Low bone density and abnormal bone turnover in patients with atherosclerosis of peripheral vessels. Osteoporos Int 15:389–395

    Article  PubMed  CAS  Google Scholar 

  39. Promislow JH, Goodman-Gruen D, Slymen DJ, Barrett-Connor E (2002) Retinol intake and bone mineral density in the elderly: the Rancho Bernardo Study. J Bone Miner Res 17:1349–1358

    Article  PubMed  CAS  Google Scholar 

  40. Reid IR, Ames RW, Evans MC, Sharpe SJ, Gamble GD (1994) Determinants of the rate of bone loss in normal postmenopausal women. J Clin Endocrinol Metab 79:950–954

    Article  PubMed  CAS  Google Scholar 

  41. Reid IR, Hague W, Emberson J, Baker J, Tonkin A, Hunt D, MacMahon S, Sharpe N (2001) Effect of pravastatin on frequency of fracture in the LIPID study: secondary analysis of a randomised controlled trial. Long-term intervention with pravastatin in ischaemic disease. Lancet 357:509–512

    Article  PubMed  CAS  Google Scholar 

  42. Rosenblat M, Aviram M (2002) Oxysterol-induced activation of macrophage NADPH-oxidase enhances cell-mediated oxidation of LDL in the atherosclerotic apolipoprotein E deficient mouse: inhibitory role for vitamin E. Atherosclerosis 160:69–80

    Article  PubMed  CAS  Google Scholar 

  43. Rozenberg O, Shih DM, Aviram M (2003) Human serum paraoxonase 1 decreases macrophage cholesterol biosynthesis: possible role for its phospholipase-A2-like activity and lysophosphatidylcholine formation. Arterioscler Thromb Vasc Biol 23:461–467

    Article  PubMed  CAS  Google Scholar 

  44. Rozenberg O, Rosenblat M, Coleman R, Shih DM, Aviram M (2003) Paraoxonase (PON1) deficiency is associated with increased macrophage oxidative stress: studies in PON1-knockout mice. Free Radic Biol Med 34:774–784

    Article  PubMed  CAS  Google Scholar 

  45. Samelson EJ, Kiel DP, Broe KE, Zhang Y, Cupples LA, Hannan MT, Wilson PW, Levy D, Williams SA, Vaccarino V (2004) Metacarpal cortical area and risk of coronary heart disease: the Framingham study. Am J Epidemiol 159:589–595

    Article  PubMed  Google Scholar 

  46. Samelson EJ, Cupples LA, Hannan MT, Wilson PW, Williams SA, Vaccarino V, Zhang Y, Kiel DP (2004) Long-term effects of serum cholesterol on bone mineral density in women and men: the Framingham Osteoporosis Study. Bone 34:557–561

    Article  PubMed  CAS  Google Scholar 

  47. Sarandol A, Sarandol E, Eker SS, Karaagac EU, Hizli BZ, Dirican M, Kirli S (2006) Oxidation of apolipoprotein B-containing lipoproteins and serum paraoxonase/arylesterase activities in major depressive disorder. Prog Neuropsychopharmacol Biol Psychiatry 30:1103–1108

    Article  PubMed  CAS  Google Scholar 

  48. Schulz E, Arfai K, Liu X, Sayre J, Gilsanz V (2004) Aortic calcification and the risk of osteoporosis and fractures. J Clin Endocrinol Metab 89:4246–4253

    Article  PubMed  CAS  Google Scholar 

  49. Shih DM, Xia YR, Wang XP, Miller E, Castellani LW, Subbanagounder G, Cheroutre H, Faull KF, Berliner JA, Witztum JL, Lusis AJ (2000) Combined serum paraoxonase knockout/apolipoprotein E knockout mice exhibit increased lipoprotein oxidation and atherosclerosis. J Biol Chem 275:17527–17535

    Article  PubMed  CAS  Google Scholar 

  50. Shiraki M, Shiraki Y, Aoki C, Hosoi T, Inoue S, Kaneki M, Ouchi Y (1997) Association of bone mineral density with apolipoprotein E phenotype. J Bone Miner Res 12:1438–1445

    Article  PubMed  CAS  Google Scholar 

  51. Singh U, Jialal I (2006) Oxidative stress and atherosclerosis. Pathophysiology [Epub ahead of print]

  52. Sinnott B, Syed I, Sevrukov A, Barengolts E (2006) Coronary calcification and osteoporosis in men and postmenopausal women are independent processes associated with aging. Calcif Tissue Int 78:195–202

    Article  PubMed  CAS  Google Scholar 

  53. Stocker R, Keaney JF Jr (2004) Role of oxidative modifications in atherosclerosis. Physiol Rev 84:1381–1478

    Article  PubMed  CAS  Google Scholar 

  54. Tanko LB, Bagger YZ, Nielsen SB, Christiansen C (2003) Does serum cholesterol contribute to vertebral bone loss in postmenopausal women? Bone 32:8–14

    Article  PubMed  CAS  Google Scholar 

  55. Tanko LB, Bagger YZ, Christiansen C (2003) Low bone mineral density in the hip as a marker of advanced atherosclerosis in elderly women. Calcif Tissue Int 73:15–20

    Article  PubMed  CAS  Google Scholar 

  56. Thomsen AB, Silvestri S, Haarbo J, Christiansen C, Bjarnason NH (2004) Associated response in bone and lipids during hormone replacement therapy. Maturitas 47:39–45

    Article  PubMed  CAS  Google Scholar 

  57. van der Klift M, Pols HA, Hak AE, Witteman JC, Hofman A, de Laet CE (2002) Bone mineral density and the risk of peripheral arterial disease: the Rotterdam Study. Calcif Tissue Int 70:443–449

    Article  PubMed  CAS  Google Scholar 

  58. van Staa TP, Wegman S, de Vries F, Leufkens B, Cooper C (2001) Use of statins and risk of fractures. JAMA 285:1850–1855

    Article  PubMed  Google Scholar 

  59. Vogt MT, San Valentin R, Forrest KYZ, Nevitt MC, Cauley JA (1997) Bone mineral density and aortic calcification: the study of osteoporotic fractures. J Am Geriatr Soc 45:140–145

    PubMed  CAS  Google Scholar 

  60. von der Recke P, Hansen MA, Hassager C (1999) The association between low bone mass at the menopause and cardiovascular mortality. Am J Med 106:273–278

    Article  PubMed  Google Scholar 

  61. Wang MC, Luz Villa M, Marcus R, Kelsey JL (1997) Associations of vitamin C, calcium, and protein with bone mass in postmenopausal Mexican American women. Osteop Int 7:533–538

    CAS  Google Scholar 

  62. Watanabe S, Fukumoto S, Takeuchi Y, Fujita H, Nakano T, Fujita T (2001) Effects of 1-year treatment with fluvastatin or pravastatin on bone. Am J Med 110:584–587

    Article  PubMed  CAS  Google Scholar 

  63. Watson AD, Navab M, Hama SY, Sevanian A, Prescott SM, Stafforini DM, McIntyre TM, Du BN, Fogelman AM, Berliner JA (1995) Effect of platelet activating factor-acetylhydrolase on the formation and action of minimally oxidized low density lipoprotein. J Clin Invest 95:774–782

    PubMed  CAS  Google Scholar 

  64. Watson AD, Berliner JA, Hama SY, La Du BN, Faull KF, Fogelman AM, Navab M (1995) Protective effect of high density lipoprotein associated paraoxonase. Inhibition of the biological activity of minimally oxidized low density lipoprotein. J Clin Invest 96:2882–2891

    Article  PubMed  CAS  Google Scholar 

  65. Wolf RL, Cauley JA, Pettinger M, Jackson R, Lacroix A, Leboff MS, Lewis CE, Nevitt MC, Simon JA, Stone KL, Wactawski-Wende J (2005) Lack of a relation between vitamin and mineral antioxidants and bone mineral density: results from the Women’s Health Initiative. Am J Clin Nutr 82:581–588

    PubMed  CAS  Google Scholar 

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Correspondence to Fatma Ferda Verit.

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Verit, F.F., Celik, H., Yazgan, P. et al. Paraoxonase-1 activity as a marker of atherosclerosis is not associated with low bone mineral density in healthy postmenopausal women. Arch Gynecol Obstet 275, 353–359 (2007). https://doi.org/10.1007/s00404-006-0260-x

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