Current Atherosclerosis Reports

, Volume 14, Issue 2, pp 101–107

High-Density Lipoprotein and Atherosclerosis: The Role of Antioxidant Activity

Coronary Heart Disease (J Farmer, Section Editor)

Abstract

Levels of high-density lipoprotein (HDL) cholesterol are generally inversely associated with the risk for the development of atherosclerosis. The mechanism by which HDL imparts protection from the initiation and progression of occlusive vascular disease is complex and multifactorial. The major anti-atherosclerotic effect of HDL is felt to be reverse cholesterol transport. HDL has been demonstrated to scavenge cholesterol from the peripheral vasculature with transport to the liver, where is it excreted in the biliary system. However, HDL exhibits multiple other physiologic effects that may play a role in the reduced risk for atherosclerosis. HDL has been demonstrated to exhibit beneficial effects on platelet function, endothelial function, coagulation parameters, inflammation, and interactions with triglyceride-rich lipoproteins. Increasing amounts of clinical and experimental data have shown that HDL cholesterol has significant antioxidant effect that may significantly contribute to protection from atherosclerosis.

Keywords

High density lipoprotein Atherosclerosis Reverse cholesterol transport Antioxidant Endothelial function 

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 1.
    Barter P, et al. HDL cholesterol, very low levels of LDL cholesterol, and cardiovascular events. N Engl J Med. 2007;357(13):1301–10.PubMedCrossRefGoogle Scholar
  2. 2.
    •• Brufau G, Groen AK, Kuipers F. Reverse cholesterol transport revisited: contribution of biliary versus intestinal cholesterol excretion. Arterioscler Thromb Vasc Biol. 2011;31(8):1726–33. This is an excellent review of alternatives mechanisms in the removal of cholesterol stores from vascular depots and subsequent excretion into the gastrointestinal tract.PubMedCrossRefGoogle Scholar
  3. 3.
    Assmann G, Gotto Jr AM. HDL cholesterol and protective factors in atherosclerosis. Circulation. 2004;109(23 Suppl 1):III8–III14.PubMedGoogle Scholar
  4. 4.
    Florentin M, et al. Multiple actions of high-density lipoprotein. Curr Opin Cardiol. 2008;23(4):370–8.PubMedCrossRefGoogle Scholar
  5. 5.
    • Williams PT, Feldman DE. Prospective study of coronary heart disease vs. HDL2, HDL3, and other lipoproteins in Gofman's Livermore Cohort. Atherosclerosis. 2011;214(1):196–202. This is an epidemiologic study that provides a mechanism and rationale for the correlation of cardiovascular risk with various HDL subfractions.PubMedCrossRefGoogle Scholar
  6. 6.
    Kontush A, Chapman MJ. Antiatherogenic function of HDL particle subpopulations: focus on antioxidative activities. Curr Opin Lipidol. 2010;21(4):312–8.PubMedCrossRefGoogle Scholar
  7. 7.
    Tall AR. Functions of cholesterol ester transfer protein and relationship to coronary artery disease risk. J Clin Lipidol. 2010;4(5):389–93.PubMedCrossRefGoogle Scholar
  8. 8.
    •• Sanz J, Fuster V. The year in atherothrombosis. J Am Coll Cardiol. 2011;58(8):779–91. This article contains comprehensive reviews of major advances over the past 12 months, including a review of multiple studies of HDL including epidemiologic correlations and studies utilizing nicotinic acid and fibric acid derivatives. Additionally, references are provided for the role of cholesterol ester transfer protein and cardiovascular outcomes. The role of HDL mimetics is also discussed.PubMedCrossRefGoogle Scholar
  9. 9.
    van Hinsbergh, V. W. Endothelium-role in regulation of coagulation and inflammation. Semin Immunopathol. 2011.Google Scholar
  10. 10.
    Turner EC, et al. Interaction of the human prostacyclin receptor with the PDZ adapter protein PDZK1: role in endothelial cell migration and angiogenesis. Mol Biol Cell. 2011;22(15):2664–79.PubMedCrossRefGoogle Scholar
  11. 11.
    Appel SJ, Harrell JS, Davenport ML. Central obesity, the metabolic syndrome, and plasminogen activator inhibitor-1 in young adults. J Am Acad Nurse Pract. 2005;17(12):535–41.PubMedCrossRefGoogle Scholar
  12. 12.
    Superko RH. Lipoprotein subclasses and atherosclerosis. Front Biosci. 2001;6:D355–65.PubMedCrossRefGoogle Scholar
  13. 13.
    Donati MB. The "common soil hypothesis": evidence from population studies? Thromb Res. 2010;125 Suppl 2:S92–5.PubMedCrossRefGoogle Scholar
  14. 14.
    Madamanchi NR, Hakim ZS, Runge MS. Oxidative stress in atherogenesis and arterial thrombosis: the disconnect between cellular studies and clinical outcomes. J Thromb Haemost. 2005;3(2):254–67.PubMedCrossRefGoogle Scholar
  15. 15.
    Bonomini F, et al. Atherosclerosis and oxidative stress. Histol Histopathol. 2008;23(3):381–90.PubMedGoogle Scholar
  16. 16.
    Nicholls SJ, et al. Reconstituted high-density lipoproteins inhibit the acute pro-oxidant and proinflammatory vascular changes induced by a periarterial collar in normocholesterolemic rabbits. Circulation. 2005;111(12):1543–50.PubMedCrossRefGoogle Scholar
  17. 17.
    Steinbrecher UP, Zhang HF, Lougheed M. Role of oxidatively modified LDL in atherosclerosis. Free Radic Biol Med. 1990;9(2):155–68.PubMedCrossRefGoogle Scholar
  18. 18.
    Stocker R, Keaney Jr JF. Role of oxidative modifications in atherosclerosis. Physiol Rev. 2004;84(4):1381–478.PubMedCrossRefGoogle Scholar
  19. 19.
    Napoli C, de Nigris F, Palinski W. Multiple role of reactive oxygen species in the arterial wall. J Cell Biochem. 2001;82(4):674–82.PubMedCrossRefGoogle Scholar
  20. 20.
    Navab M, et al. The oxidation hypothesis of atherogenesis: the role of oxidized phospholipids and HDL. J Lipid Res. 2004;45(6):993–1007.PubMedCrossRefGoogle Scholar
  21. 21.
    Negre-Salvayre A, et al. Antioxidant and cytoprotective properties of high-density lipoproteins in vascular cells. Free Radic Biol Med. 2006;41(7):1031–40.PubMedCrossRefGoogle Scholar
  22. 22.
    Kunitake ST, et al. Binding of transition metals by apolipoprotein A-I-containing plasma lipoproteins: inhibition of oxidation of low density lipoproteins. Proc Natl Acad Sci U S A. 1992;89(15):6993–7.PubMedCrossRefGoogle Scholar
  23. 23.
    Klimov AN, et al. On the ability of high density lipoproteins to remove phospholipid peroxidation products from erythrocyte membranes. Biochemistry (Mosc). 2001;66(3):300–4.CrossRefGoogle Scholar
  24. 24.
    Ribas V, et al. Human apolipoprotein A-II enrichment displaces paraoxonase from HDL and impairs its antioxidant properties: a new mechanism linking HDL protein composition and antiatherogenic potential. Circ Res. 2004;95(8):789–97.PubMedCrossRefGoogle Scholar
  25. 25.
    Garner B, et al. Oxidation of high density lipoproteins. II. Evidence for direct reduction of lipid hydroperoxides by methionine residues of apolipoproteins AI and AII. J Biol Chem. 1998;273(11):6088–95.PubMedCrossRefGoogle Scholar
  26. 26.
    Chiesa G, Sirtori CR. Apolipoprotein A-I(Milano): current perspectives. Curr Opin Lipidol. 2003;14(2):159–63.PubMedCrossRefGoogle Scholar
  27. 27.
    Nissen SE, et al. Effect of recombinant ApoA-I Milano on coronary atherosclerosis in patients with acute coronary syndromes: a randomized controlled trial. JAMA. 2003;290(17):2292–300.PubMedCrossRefGoogle Scholar
  28. 28.
    •• Degoma EM, Rader DJ. Novel HDL-directed pharmacotherapeutic strategies. Nat Rev Cardiol. 2011;8(5):266–77. This is an excellent and comprehensive review of the role of HDL-directed therapies in the prevention of cardiovascular disease. Multiple approaches such as direct or indirect mechanisms to augment Apo A1 levels, utilization of nicotinic acid receptor agonists, endothelial lipase inhibitors, and mimicking of Apo A1 functionality are reviewed in detail. Mechanisms to enhance reverse cholesterol transport are also presented.PubMedCrossRefGoogle Scholar
  29. 29.
    Mackness MI, et al. Serum paraoxonase activity in familial hypercholesterolaemia and insulin-dependent diabetes mellitus. Atherosclerosis. 1991;86(2–3):193–9.PubMedCrossRefGoogle Scholar
  30. 30.
    Mackness B, et al. Serum paraoxonase activity in patients with type 1 diabetes compared to healthy controls. Eur J Clin Invest. 2002;32(4):259–64.PubMedCrossRefGoogle Scholar
  31. 31.
    Precourt LP, et al. The three-gene paraoxonase family: physiologic roles, actions and regulation. Atherosclerosis. 2011;214(1):20–36.PubMedCrossRefGoogle Scholar
  32. 32.
    Navab M, et al. HDL and the inflammatory response induced by LDL-derived oxidized phospholipids. Arterioscler Thromb Vasc Biol. 2001;21(4):481–8.PubMedCrossRefGoogle Scholar
  33. 33.
    Yost CC, Weyrich AS, Zimmerman GA. The platelet activating factor (PAF) signaling cascade in systemic inflammatory responses. Biochimie. 2010;92(6):692–7.PubMedCrossRefGoogle Scholar
  34. 34.
    Penna C, Bassino E, Alloatti G. Platelet activating factor: the good and the bad in the ischemic/reperfused heart. Exp Biol Med (Maywood). 2011;236(4):390–401.CrossRefGoogle Scholar
  35. 35.
    Tselepis AD, John M. Chapman, Inflammation, bioactive lipids and atherosclerosis: potential roles of a lipoprotein-associated phospholipase A2, platelet activating factor-acetylhydrolase. Atheroscler Suppl. 2002;3(4):57–68.PubMedCrossRefGoogle Scholar
  36. 36.
    Costa LG, et al. Modulation of paraoxonase (PON1) activity. Biochem Pharmacol. 2005;69(4):541–50.PubMedCrossRefGoogle Scholar
  37. 37.
    Salvayre R, et al. Oxidized low-density lipoprotein-induced apoptosis. Biochim Biophys Acta. 2002;1585(2–3):213–21.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  1. 1.Department of MedicineBaylor College of MedicineHoustonUSA

Personalised recommendations