Skip to main content

Advertisement

SpringerLink
Log in

The role of paraoxonase (PON) enzyme in the extent and severity of the coronary artery disease in type-2 diabetic patients

  • ORIGINAL ARTICLE
  • Published:
Heart and Vessels Aims and scope Submit manuscript

Abstract

Increased coronary artery disease (CAD) risk is well established in diabetes mellitus (DM). Paraoxonase (PON) enzyme is known to have protective effects on lipid peroxidation. This study aimed to investigate the changes in PON activity levels with duration of DM as well as the role of PON activity in progression of CAD. Eighty-four consecutive diabetic patients (mean age 58 years, 46 men) who underwent coronary angiography for diagnostic purposes were examined. Before the angiography, fasting venous blood samples were taken for PON enzyme activity, thiobarbituric acid reactive substances (TBARS), and routine biochemical parameters. Severity and extent of coronary atherosclerosis were scored numerically using the Gensini scoring system. The population was divided into three groups according to Gensini score: Group 1, mild CAD; Group 2, moderate CAD; Group 3, severe CAD. Group 1 had higher PON levels and shorter DM duration than those of Group 3. Gensini score was significantly correlated with, PON activity (r = −0.361) and apo-AI (r = −0.375). TBARS (r = −0.290) and the duration of DM (r = −0.336) also showed a significant correlation with PON activity levels. Also, multivariate linear regression and Pearson correlation analyses showed that PON activity (P = 0.04), apo-AI levels (P = 0.01), and the duration of DM (P = 0.003) were significantly associated with Gensini score. Paraoxonase activity decreases parallel to DM duration. The lack of protective effect of PON enzyme on lipid peroxidation may be a factor in acceleration of CAD in DM.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. JR Sowers (1998) ArticleTitleDiabetes mellitus and cardiovascular disease in women Arch Intern Med 158 617–621 Occurrence Handle9521226 Occurrence Handle10.1001/archinte.158.6.617 Occurrence Handle1:STN:280:DyaK1c7otVGhsA%3D%3D

    Article  PubMed  CAS  Google Scholar 

  2. WB Kannel (1987) ArticleTitleMetabolic risk factors for coronary heart disease in women: perspective from the Framingham Study Am Heart J 114 413–419 Occurrence Handle3604900 Occurrence Handle10.1016/0002-8703(87)90511-4 Occurrence Handle1:STN:280:BiiB28jisl0%3D

    Article  PubMed  CAS  Google Scholar 

  3. InstitutionalAuthorNameAmerican Diabetes Association (1998) ArticleTitleConsensus Development Conference on the Diagnosis of Coronary Heart Disease in People with Diabetes. Miami, Florida, 10–11 February, 1998 Diabetes Care 21 1551–1559 Occurrence Handle10.2337/diacare.21.9.1551

    Article  Google Scholar 

  4. KK Griendling RW Alexander (1997) ArticleTitleOxidative stress and cardiovascular disease Circulation 96 3264–3265 Occurrence Handle9396412 Occurrence Handle1:STN:280:DyaK1c%2FlslSqug%3D%3D

    PubMed  CAS  Google Scholar 

  5. M Aviram (2000) ArticleTitleReview of human studies on oxidative damage and antioxidant protection related to cardiovascular diseases Free Radic Res 33 S85–S97 Occurrence Handle11191279 Occurrence Handle1:CAS:528:DC%2BD3MXjtVSntw%3D%3D

    PubMed  CAS  Google Scholar 

  6. GM Chisolm KC Irwin MS Penn (1992) ArticleTitleLipoprotein oxidation and lipoprotein-induced cell injury in diabetes Diabetes 41 61–66 Occurrence Handle1526338 Occurrence Handle1:CAS:528:DyaK3sXnvVSktw%3D%3D

    PubMed  CAS  Google Scholar 

  7. M Aviram (2004) ArticleTitleIntroduction to the serial review on paraoxonases, oxidative stress, and cardiovascular diseases Free Radic Biol Med 37 1301–1303 Occurrence Handle15454270 Occurrence Handle10.1016/j.freeradbiomed.2004.07.009 Occurrence Handle1:CAS:528:DC%2BD2cXnvFaiu70%3D

    Article  PubMed  CAS  Google Scholar 

  8. B Mackness MI Mackness S Arrol W Turkie PN Durington (1998) ArticleTitleEffect of the human serum paraoxonase 55 and 192 genetic polymorphisms on the protection by high density lipoprotein against low density lipoprotein oxidative modification FEBS Lett 423 57–60 Occurrence Handle9506841 Occurrence Handle10.1016/S0014-5793(98)00064-7 Occurrence Handle1:CAS:528:DyaK1cXhtVWgtrw%3D

    Article  PubMed  CAS  Google Scholar 

  9. JG Wheeler BD Keavney H Watkins R Collins J Danesh (2004) ArticleTitleFour paraoxonase gene polymorphisms in 11 212 cases of coronary heart disease and 12 786 controls: meta-analysis of 43 studies Lancet 363 689–695 Occurrence Handle15001326 Occurrence Handle10.1016/S0140-6736(04)15642-0 Occurrence Handle1:CAS:528:DC%2BD2cXhs12jur8%3D

    Article  PubMed  CAS  Google Scholar 

  10. GP Jarvik LS Rozek VH Brophy TS Hatsukami RJ Richter GD Schellenberg CE Furlong (2000) ArticleTitleParaoxonase (PON1) phenotype is a better predictor of vascular disease than is PON1192 or PON155 genotype Arterioscler Thromb Vasc Biol 20 2441–2447 Occurrence Handle11073850 Occurrence Handle1:CAS:528:DC%2BD3cXptVSisLY%3D

    PubMed  CAS  Google Scholar 

  11. B Mackness GK Davies W Turkie E Lee DH Roberts E Hill C Roberts PN Durrington MI Mackness (2001) ArticleTitleParaoxonase status in coronary heart disease. Are activity and concentration more important than genotype? Arterioscler Thromb Vasc Biol 21 1451–1457 Occurrence Handle11557671 Occurrence Handle1:CAS:528:DC%2BD3MXntVGku70%3D

    PubMed  CAS  Google Scholar 

  12. MI Mackness D Harty D Bhatnagar PH Winocour S Arrol M Ishola PN Durington (1991) ArticleTitleSerum paraoxonase activity in familial hypercholesterolaemia and insulin-dependent diabetes mellitus Atherosclerosis 86 193–199 Occurrence Handle1651732 Occurrence Handle10.1016/0021-9150(91)90215-O Occurrence Handle1:STN:280:By6A3sjitV0%3D

    Article  PubMed  CAS  Google Scholar 

  13. CA Abbott MI Mackness S Kumar AJ Boulton PN Durrington (1995) ArticleTitleSerum paraoxonase activity, concentration, and phenotype distribution in diabetes mellitus and its relationship to serum lipids and lipoproteins Arterioscler Thromb Vasc Biol 15 1812–1818 Occurrence Handle7583560 Occurrence Handle1:CAS:528:DyaK28XhslChuw%3D%3D

    PubMed  CAS  Google Scholar 

  14. KG Alberti PZ Zimmet (1998) ArticleTitleDefinition, diagnosis and classification of diabetes mellitus and its complications. Part 1: diagnosis and classification of diabetes mellitus provisional report of a WHO consultation Diabet Med 15 539–553 Occurrence Handle9686693 Occurrence Handle10.1002/(SICI)1096-9136(199807)15:7<539::AID-DIA668>3.0.CO;2-S Occurrence Handle1:STN:280:DyaK1czkvFCrsA%3D%3D

    Article  PubMed  CAS  Google Scholar 

  15. SJ Kalbfleisch MJ McGillem IM Pinto KM Kavanaugh SF DeBoe GB Mancini (1990) ArticleTitleComparison of automated quantitative coronary angiography with caliper measurements of percent diameter stenosis Am J Cardiol 65 1181–1184 Occurrence Handle2337026 Occurrence Handle10.1016/0002-9149(90)90970-C Occurrence Handle1:STN:280:By%2BB2cjivV0%3D

    Article  PubMed  CAS  Google Scholar 

  16. GG Gensini (1983) ArticleTitleA more meaningful scoring system for determining the severity of coronary heart disease Am J Cardiol 51 606 Occurrence Handle6823874 Occurrence Handle10.1016/S0002-9149(83)80105-2 Occurrence Handle1:STN:280:BiyC38zotFE%3D

    Article  PubMed  CAS  Google Scholar 

  17. CE Furlong RJ Richter SL Seidel LG Costa AG Motulsky (1989) ArticleTitleSpectrophotometric assays for the enzymatic hydrolysis of the active metabolites of chlorpyrifos and parathion by plasma paraoxonase/arylesterase Anal Biochem 180 242–247 Occurrence Handle2479288 Occurrence Handle10.1016/0003-2697(89)90424-7 Occurrence Handle1:CAS:528:DyaL1MXlvV2qtrY%3D

    Article  PubMed  CAS  Google Scholar 

  18. K Yagi (1998) ArticleTitleSimple assay for the level of total lipid peroxides in serum or plasma Methods Mol Biol 108 101–106 Occurrence Handle9921519 Occurrence Handle1:CAS:528:DyaK1cXlsFGhsL8%3D

    PubMed  CAS  Google Scholar 

  19. I Tkac BP Kimball G Lewis K Uffelman G Steiner (1997) ArticleTitleThe severity of coronary atherosclerosis in type 2 diabetes mellitus is related to the number of circulating triglyceride-rich lipoprotein particles Atheroscler Thromb Vasc Biol 17 3633–3638 Occurrence Handle1:STN:280:DyaK1c%2FpvFylsw%3D%3D

    CAS  Google Scholar 

  20. B Fuhrman L Koren N Volkova S Keidar T Hayek M Aviram (2002) ArticleTitleAtorvastatin therapy in hypercholesterolemic patients suppresses cellular uptake of oxidized-LDL by differentiating monocytes Atherosclerosis 164 179–185 Occurrence Handle12119208 Occurrence Handle10.1016/S0021-9150(02)00063-1 Occurrence Handle1:CAS:528:DC%2BD38Xlt12lt7c%3D

    Article  PubMed  CAS  Google Scholar 

  21. M Tomas M Senti F Garcia-Faria J Vila A Torrents M Covas J Marrugat (2000) ArticleTitleEffect of simvastatin therapy on paraoxonase activity and related proteins in FH patients Arterioscler Thromb Vasc Biol 20 2113–2119 Occurrence Handle10978257 Occurrence Handle1:CAS:528:DC%2BD3cXntV2itLw%3D

    PubMed  CAS  Google Scholar 

  22. S Wassmann U Laufs K Muller C Konkol K Ahlbory AT Baumer W Linz M Bohm G Nickening (2002) ArticleTitleCellular antioxidant effects of atorvastatin in-vitro and in-vivo Arterioscler Thromb Vasc Biol 22 300–305 Occurrence Handle11834532 Occurrence Handle10.1161/hq0202.104081 Occurrence Handle1:CAS:528:DC%2BD38Xhtlyjsbg%3D

    Article  PubMed  CAS  Google Scholar 

  23. DM Shih YR Xia XP Wang E Miller LW Castellani G Subbanagounder H Cheroutre KF Faull JA Berliner JL Witztum AJ Luis (2000) ArticleTitleCombined serum paraoxonase knockout/apolipoprotein E knockout mice exhibit increased lipoprotein oxidation and atherosclerosis J Biol Chem 275 17527–17535 Occurrence Handle10748217 Occurrence Handle10.1074/jbc.M910376199 Occurrence Handle1:CAS:528:DC%2BD3cXktFaksbk%3D

    Article  PubMed  CAS  Google Scholar 

  24. EM Rubin RM Krauss EA Spangler JG Verstuyft SM Clift (1991) ArticleTitleInhibition of early atherogenesis in transgenic mice by human apolipoprotein AI Nature 353 265–267 Occurrence Handle1910153 Occurrence Handle10.1038/353265a0 Occurrence Handle1:CAS:528:DyaK3MXmtVKrsL0%3D

    Article  PubMed  CAS  Google Scholar 

  25. RC Sorenson CL Bisgaier M Aviram C Hsu S Billecke BN La Du (1999) ArticleTitleHuman serum Paraoxonase/arylesterase's retained hydrophobic N-terminal leader sequence associates with HDLs by binding phospholipids: apolipoprotein A-I stabilizes activity Arterioscler Thromb Vasc Biol 19 2214–2225 Occurrence Handle10479665 Occurrence Handle1:CAS:528:DyaK1MXmtFOrtLw%3D

    PubMed  CAS  Google Scholar 

  26. MC Phillips KL Gillotte MP Haynes WJ Johnson S Lund-Katz GH Rothblat (1998) ArticleTitleMechanisms of high density lipoprotein-mediated efflux of cholesterol from cell plasma membranes Atherosclerosis 137 IssueIDSuppl S13–17 Occurrence Handle9694536 Occurrence Handle10.1016/S0021-9150(97)00312-2 Occurrence Handle1:CAS:528:DyaK1cXivVCmtb8%3D

    Article  PubMed  CAS  Google Scholar 

  27. E Nobecourt S Jacqueminet B Hansel S Chantepie A Grimaldi MJ Chapman A Kontush (2005) ArticleTitleDefective antioxidative activity of small dense HDL3 particles in type 2 diabetes: relationship to elevated oxidative stress and hyperglycaemia Diabetologia 48 529–538 Occurrence Handle15729582 Occurrence Handle10.1007/s00125-004-1655-5 Occurrence Handle1:CAS:528:DC%2BD2MXisVCitbg%3D

    Article  PubMed  CAS  Google Scholar 

  28. MI Mackness S Arrol C Abbott PN Durrington (1993) ArticleTitleProtection of low-density lipoprotein against oxidative modification by high-density lipoprotein associated paraoxonase Atherosclerosis 104 129–135 Occurrence Handle8141836 Occurrence Handle10.1016/0021-9150(93)90183-U Occurrence Handle1:CAS:528:DyaK2cXlvFylsbo%3D

    Article  PubMed  CAS  Google Scholar 

  29. CC Hedrick SR Thorpe MX Fu CM Harper J Yoo SM Kim H Wong AL Peters (2000) ArticleTitleGlycation impairs high-density lipoprotein function Diabetologia 43 312–320 Occurrence Handle10768092 Occurrence Handle10.1007/s001250050049 Occurrence Handle1:CAS:528:DC%2BD3cXhsFylur8%3D

    Article  PubMed  CAS  Google Scholar 

  30. MI Mackness S Arrol PN Durrington (1991) ArticleTitleParaoxonase prevents accumulation of lipoperoxides in low-density lipoprotein FEBS Lett 286 152–154 Occurrence Handle1650712 Occurrence Handle10.1016/0014-5793(91)80962-3 Occurrence Handle1:CAS:528:DyaK3MXltFWgu7Y%3D

    Article  PubMed  CAS  Google Scholar 

  31. Y Ikeda T Suehiro M Inoue Y Nakauchi T Morita K Arii H Ito Y Kumon K Hashimoto (1998) ArticleTitleSerum paraoxonase activity and its relationship to diabetic complications in patients with non-insulin-dependent diabetes mellitus Metabolism 47 598–602 Occurrence Handle9591753 Occurrence Handle10.1016/S0026-0495(98)90246-3 Occurrence Handle1:CAS:528:DyaK1cXjtFertb8%3D

    Article  PubMed  CAS  Google Scholar 

  32. SP Wolff ZY Jiang JV Hunt (1991) ArticleTitleProtein glycation and oxidative stress in diabetes mellitus and ageing Free Radic Biol Med 10 339–352 Occurrence Handle1855674 Occurrence Handle10.1016/0891-5849(91)90040-A Occurrence Handle1:CAS:528:DyaK3MXktVKjsrY%3D

    Article  PubMed  CAS  Google Scholar 

  33. J Nourooz-Zadeh J Tajaddini-Sarmadi S McCarthy DJ Betteridge SP Wolff (1995) ArticleTitleElevated levels of authentic plasma hydroperoxides in NIDDM Diabetes 44 1054–1058 Occurrence Handle7657028 Occurrence Handle10.2337/diabetes.44.9.1054 Occurrence Handle1:CAS:528:DyaK2MXotVGhurY%3D

    Article  PubMed  CAS  Google Scholar 

  34. B Agaçhan H Yilmaz HA Ergen ZE Karaali T Isbir (2005) ArticleTitleParaoxonase (PON1) 55 and 192 Polymorphism and Its Effects to Oxidant-Antioxidant System in Turkish Patients with Type 2 Diabetes Mellitus Physiol Res 54 287–293 Occurrence Handle15974833

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Cardiology, Siyami Ersek Cardiovascular and Thoracic Surgery Centre, Istanbul, Turkey

    Zeynep Tartan, Gokcen Orhan, Hulya Kasıkçioglu, Huseyin Uyarel, Sennur Unal, Nihat Ozer & Nese Cam

  2. Department of Cardiovascular Surgery, Siyami Ersek Cardiovascular and Thoracic Surgery Centre, Istanbul, Turkey

    Gokcen Orhan & Batuhan Ozay

  3. GenLab Genetic Medical Laboratories, Istanbul, Turkey

    Figen Ciloglu

Authors
  1. Zeynep Tartan
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Gokcen Orhan
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Hulya Kasıkçioglu
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Huseyin Uyarel
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Sennur Unal
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Nihat Ozer
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Batuhan Ozay
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Figen Ciloglu
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Nese Cam
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Zeynep Tartan.

Additional information

This study was presented as a poster in at the International Symposium on Atherosclerosis Rome, Italy, June 18–22, 2006.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Tartan, Z., Orhan, G., Kasıkçioglu, H. et al. The role of paraoxonase (PON) enzyme in the extent and severity of the coronary artery disease in type-2 diabetic patients. Heart Vessels 22, 158–164 (2007). https://doi.org/10.1007/s00380-006-0957-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00380-006-0957-6

Key words

Search

Navigation