Advertisement

High-density lipoproteins: the guardian angel of the cell membrane

  • G. Ferretti
  • T. Bacchetti
  • S. Masciangelo
  • E. Bertoli
Review
  • 31 Downloads

Abstract

High-density lipoproteins (HDL) plasma levels are inversely correlated with the risk of atherosclerosis and coronary heart disease. The protective effect of HDL has been related to their role in the cholesterol reverse transport and to their ability to inhibit oxidation of low-density lipoproteins (LDL). Several lines of evidence suggest that the protective effect of HDL is at least partially related to the enzyme paraoxonase (PON1), a calcium-dependent esterase associated with the HDL surface. It has been hypothesised that PON1 may have two independent antiatherogenic roles: (a) by preventing the accumulation of oxidised lipids from oxidised lipoproteins (LDL and HDL) and thereby inhibiting the atherogenic and inflammatory response induced by lipid peroxidation products; (b) by detoxifying homocysteine thiolactone (HTL), a toxic metabolite of homocysteine. Recently, it has been reported that HDL-associated PON1 could also play a regulatory role in HDL binding to cell membranes and in HDL-mediated cholesterol efflux in macrophages. Several papers have reported that HDL are also able to protect and/or repair oxidative damage of cell membranes and we have recently demonstrated that the protective role of HDL is related to PON1 activity.

Keywords

Antioxidant Cardiovascular disease High-density lipoproteins (HDL) Homocysteine thiolactone (HTL) Low-density lipoproteins (LDL) Oxidative stress Paraoxonase (PON1) 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Calvert GD, Abbey M (1985) Plasma lipoproteins, apolipoproteins, and proteins concerned with lipid metabolism. Adv Clin Chem 24:217–298CrossRefGoogle Scholar
  2. 2.
    Assmann G, Nofer JR (2003) Atheroprotective effects of high density lipoproteins. Annu Rev Med 54:321–341CrossRefGoogle Scholar
  3. 3.
    Qiao Q, Gao W, Zhang L et al (2007) Metabolic syndrome and cardiovascular disease. Ann Clin Biochem 44:232–263CrossRefGoogle Scholar
  4. 4.
    Ferretti G, Bacchetti T, Busni D et al (2004) Protective effect of paraoxonase activity in high-density lipoproteins against erythrocyte membranes peroxidation: a comparison between healthy subjects and type 1 diabetic patients. J Clin Endocrinol Metab 89:2957–2962CrossRefGoogle Scholar
  5. 5.
    Quijada Z, Paoli M, Zerpa Y et al (2008) The triglyceride/HDL-cholesterol ratio as a marker of cardiovascular risk in obese children; association with traditional and emergent risk factors. Pediatr Diabetes 9:464–471CrossRefGoogle Scholar
  6. 6.
    Genest J, McNamara J, Salem D, Schaefer E (1991) Prevalence of risk factors in men with premature coronary artery disease. Am J Cardiol 67:1185–1189CrossRefGoogle Scholar
  7. 7.
    Negre-Salvayre A, Dousset N, Ferretti G et al (2006) Antioxidant and cytoprotective properties of high-density lipoproteins in vascular cells. Free Radic Biol Med 41:1031–1040CrossRefGoogle Scholar
  8. 8.
    Navab M, Yu R, Gharavi N et al (2007) High-density lipoprotein: antioxidant and anti-inflammatory properties. Curr Atheroscler Rep 9:244–248CrossRefGoogle Scholar
  9. 9.
    Yoshikawa M, Sakuma N, Hibino T et al (1997) HDL3 exerts more powerful anti-oxidative, protective effects against copper-catalyzed LDL oxidation than HDL2. Clin Biochem 30:221–225CrossRefGoogle Scholar
  10. 10.
    Klimov AN, Gurevich VS, Nikiforova AA et al (1993) Antioxidative activity of high density lipoproteins in vivo. Atherosclerosis 100:13–18CrossRefGoogle Scholar
  11. 11.
    Mackness MI, Arrol S, Abbott C, Durrington PN (1993) Protection of low-density lipoprotein against oxidative modification by high-density lipoprotein associated paraoxonase. Atherosclerosis 104:129–135CrossRefGoogle Scholar
  12. 12.
    Mackness MI, Durrington PN (1995) HDL, its enzymes and its potential to influence lipid peroxidation. Atherosclerosis 115:243–253CrossRefGoogle Scholar
  13. 13.
    Watson AD, Berliner JA, Hama SY et al (1995) Protective effect of high density lipoprotein associated paraoxonase. Inhibition of the biological activity of minimally oxidized low density lipoprotein. J Clin Invest 96:2882–2891CrossRefGoogle Scholar
  14. 14.
    Aviram M, Rosenblat M (2005) Paraoxonases and cardiovascular diseases: pharmacological and nutritional influences. Curr Opin Lipidol 16:393–399CrossRefGoogle Scholar
  15. 15.
    Ferretti G, Bacchetti T, Moroni C et al (2005) Paraoxonase activity in high-density lipoproteins: a comparison between healthy and obese females. J Clin Endocrinol Metab 90:1728–1733CrossRefGoogle Scholar
  16. 16.
    Mackness MI, Harty D, Bhatnagar D et al (1991) Serum paraoxonase activity in familial hypercholesterolaemia and insulin-dependent diabetes mellitus. Atherosclerosis 86:193–199CrossRefGoogle Scholar
  17. 17.
    Ferretti G, Bacchetti T, Masciangelo S, Pallotta G (2008) Lipid peroxidation in hemodialysis patients: effect of vitamin C supplementation. Clin Biochem 41:381–386CrossRefGoogle Scholar
  18. 18.
    Ayub A, Mackness MI, Arrol S et al (1999) Serum paraoxonase after myocardial infarction. Arterioscler Thromb Vasc Biol 19:330–335Google Scholar
  19. 19.
    Ferretti G, Bacchetti T, Principi F et al (2005) Increased levels of lipid hydroperoxides in plasma of patients with multiple sclerosis: a relationship with paraoxonase activity. Mult Scler 11:677–682CrossRefGoogle Scholar
  20. 20.
    Shih DM, Gu L, Xia YR et al (1998) Mice lacking serum paraoxonase are susceptible to organophosphate toxicity and atherosclerosis. Nature 394:284–287CrossRefGoogle Scholar
  21. 21.
    Tward A, Xia YR, Wang XP et al (2002) Decreased atherosclerotic lesion formation in human serum paraoxonase transgenic mice. Circulation 106:484–490CrossRefGoogle Scholar
  22. 22.
    van Himbergen TM, van der Schouw YT, Voorbij HA et al (2008) Paraoxonase (PON1) and the risk for coronary heart disease and myocardial infarction in a general population of Dutch women. Atherosclerosis 199:408–414CrossRefGoogle Scholar
  23. 23.
    Sentürk T, Sarandöl E, Güllülü S et al (2008) Association between paraoxonase 1 activity and severity of coronary artery disease in patients with acute coronary syndromes. Acta Cardiol 63:361–367CrossRefGoogle Scholar
  24. 24.
    Klimov AN, Kozhevnikova KA, Kuzmin AA et al (2001) On the ability of high density lipoproteins to remove phospholipid peroxidation products from erythrocyte membranes. Biochemistry (Mosc) 66:300–304CrossRefGoogle Scholar
  25. 25.
    Ferretti G, Bacchetti T, Moroni C et al (2003) Copper-induced oxidative damage on astrocytes: protective effect exerted by human high density lipoproteins. Biochim Biophys Acta 1635:48–54Google Scholar
  26. 26.
    Rosenblat M, Vaya J, Shih D, Aviram M (2005) Paraoxonase 1 (PON1) enhances HDL-mediated macrophage cholesterol efflux via the ABCA1 transporter in association with increased HDL binding to the cells: a possible role for lysophosphatidylcholine. Atherosclerosis 179:69–77CrossRefGoogle Scholar
  27. 27.
    Efrat M, Aviram M (2008) Macrophage paraoxonase 1 (PON1) binding sites. Biochem Biophys Res Commun 376:105–110CrossRefGoogle Scholar
  28. 28.
    Bowry VW, Stanley KK, Stocker R (2002) High density lipoprotein is the major carrier of lipid hydroperoxides in human blood plasma from fasting donors. Proc Natl Acad Sci U S A 89:10316–10320CrossRefGoogle Scholar
  29. 29.
    Jakubowski H (2000) Calcium-dependent human serum homocysteine thiolactone hydrolase. A protective mechanism against protein N-homocysteinylation. J Biol Chem 275:3957–3962CrossRefGoogle Scholar
  30. 30.
    Jakubowski H (2002) Homocysteine is a protein amino acid in humans. Implications for homocysteine-linked disease. J Biol Chem 277:30425–30428CrossRefGoogle Scholar
  31. 31.
    Ferretti G, Bacchetti T, Moroni C et al (2004) Effect of homocysteinylation of low density lipoproteins on lipid peroxidation of human endothelial cells. J Cell Biochem 92:351–360CrossRefGoogle Scholar

Copyright information

© Springer-Verlag Italia 2009

Authors and Affiliations

  • G. Ferretti
    • 1
  • T. Bacchetti
    • 1
  • S. Masciangelo
    • 1
  • E. Bertoli
    • 1
  1. 1.Post Graduate School of Nutrition, Institute of Biochemistry Faculty of MedicinePolytechnic University of MarcheAnconaItaly

Personalised recommendations