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Published in: Current Atherosclerosis Reports 2/2012

01-04-2012 | Coronary Heart Disease (J Farmer, Section Editor)

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

Authors: Salman Bandeali, John Farmer

Published in: Current Atherosclerosis Reports | Issue 2/2012

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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.
Literature
1.
go back to reference Barter P, et al. HDL cholesterol, very low levels of LDL cholesterol, and cardiovascular events. N Engl J Med. 2007;357(13):1301–10.PubMedCrossRef Barter P, et al. HDL cholesterol, very low levels of LDL cholesterol, and cardiovascular events. N Engl J Med. 2007;357(13):1301–10.PubMedCrossRef
2.
go back to reference •• 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.PubMedCrossRef •• 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.PubMedCrossRef
3.
go back to reference Assmann G, Gotto Jr AM. HDL cholesterol and protective factors in atherosclerosis. Circulation. 2004;109(23 Suppl 1):III8–III14.PubMed Assmann G, Gotto Jr AM. HDL cholesterol and protective factors in atherosclerosis. Circulation. 2004;109(23 Suppl 1):III8–III14.PubMed
4.
go back to reference Florentin M, et al. Multiple actions of high-density lipoprotein. Curr Opin Cardiol. 2008;23(4):370–8.PubMedCrossRef Florentin M, et al. Multiple actions of high-density lipoprotein. Curr Opin Cardiol. 2008;23(4):370–8.PubMedCrossRef
5.
go back to reference • 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.PubMedCrossRef • 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.PubMedCrossRef
6.
go back to reference Kontush A, Chapman MJ. Antiatherogenic function of HDL particle subpopulations: focus on antioxidative activities. Curr Opin Lipidol. 2010;21(4):312–8.PubMedCrossRef Kontush A, Chapman MJ. Antiatherogenic function of HDL particle subpopulations: focus on antioxidative activities. Curr Opin Lipidol. 2010;21(4):312–8.PubMedCrossRef
7.
go back to reference Tall AR. Functions of cholesterol ester transfer protein and relationship to coronary artery disease risk. J Clin Lipidol. 2010;4(5):389–93.PubMedCrossRef Tall AR. Functions of cholesterol ester transfer protein and relationship to coronary artery disease risk. J Clin Lipidol. 2010;4(5):389–93.PubMedCrossRef
8.
go back to reference •• 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.PubMedCrossRef •• 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.PubMedCrossRef
9.
go back to reference van Hinsbergh, V. W. Endothelium-role in regulation of coagulation and inflammation. Semin Immunopathol. 2011. van Hinsbergh, V. W. Endothelium-role in regulation of coagulation and inflammation. Semin Immunopathol. 2011.
10.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
11.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
12.
13.
go back to reference Donati MB. The "common soil hypothesis": evidence from population studies? Thromb Res. 2010;125 Suppl 2:S92–5.PubMedCrossRef Donati MB. The "common soil hypothesis": evidence from population studies? Thromb Res. 2010;125 Suppl 2:S92–5.PubMedCrossRef
14.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
15.
go back to reference Bonomini F, et al. Atherosclerosis and oxidative stress. Histol Histopathol. 2008;23(3):381–90.PubMed Bonomini F, et al. Atherosclerosis and oxidative stress. Histol Histopathol. 2008;23(3):381–90.PubMed
16.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
17.
go back to reference Steinbrecher UP, Zhang HF, Lougheed M. Role of oxidatively modified LDL in atherosclerosis. Free Radic Biol Med. 1990;9(2):155–68.PubMedCrossRef Steinbrecher UP, Zhang HF, Lougheed M. Role of oxidatively modified LDL in atherosclerosis. Free Radic Biol Med. 1990;9(2):155–68.PubMedCrossRef
18.
go back to reference Stocker R, Keaney Jr JF. Role of oxidative modifications in atherosclerosis. Physiol Rev. 2004;84(4):1381–478.PubMedCrossRef Stocker R, Keaney Jr JF. Role of oxidative modifications in atherosclerosis. Physiol Rev. 2004;84(4):1381–478.PubMedCrossRef
19.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
20.
go back to reference Navab M, et al. The oxidation hypothesis of atherogenesis: the role of oxidized phospholipids and HDL. J Lipid Res. 2004;45(6):993–1007.PubMedCrossRef Navab M, et al. The oxidation hypothesis of atherogenesis: the role of oxidized phospholipids and HDL. J Lipid Res. 2004;45(6):993–1007.PubMedCrossRef
21.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
22.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
23.
go back to reference 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.CrossRef 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.CrossRef
24.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
25.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
26.
go back to reference Chiesa G, Sirtori CR. Apolipoprotein A-I(Milano): current perspectives. Curr Opin Lipidol. 2003;14(2):159–63.PubMedCrossRef Chiesa G, Sirtori CR. Apolipoprotein A-I(Milano): current perspectives. Curr Opin Lipidol. 2003;14(2):159–63.PubMedCrossRef
27.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
28.
go back to reference •• 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.PubMedCrossRef •• 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.PubMedCrossRef
29.
go back to reference Mackness MI, et al. Serum paraoxonase activity in familial hypercholesterolaemia and insulin-dependent diabetes mellitus. Atherosclerosis. 1991;86(2–3):193–9.PubMedCrossRef Mackness MI, et al. Serum paraoxonase activity in familial hypercholesterolaemia and insulin-dependent diabetes mellitus. Atherosclerosis. 1991;86(2–3):193–9.PubMedCrossRef
30.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
31.
go back to reference Precourt LP, et al. The three-gene paraoxonase family: physiologic roles, actions and regulation. Atherosclerosis. 2011;214(1):20–36.PubMedCrossRef Precourt LP, et al. The three-gene paraoxonase family: physiologic roles, actions and regulation. Atherosclerosis. 2011;214(1):20–36.PubMedCrossRef
32.
go back to reference Navab M, et al. HDL and the inflammatory response induced by LDL-derived oxidized phospholipids. Arterioscler Thromb Vasc Biol. 2001;21(4):481–8.PubMedCrossRef Navab M, et al. HDL and the inflammatory response induced by LDL-derived oxidized phospholipids. Arterioscler Thromb Vasc Biol. 2001;21(4):481–8.PubMedCrossRef
33.
go back to reference Yost CC, Weyrich AS, Zimmerman GA. The platelet activating factor (PAF) signaling cascade in systemic inflammatory responses. Biochimie. 2010;92(6):692–7.PubMedCrossRef Yost CC, Weyrich AS, Zimmerman GA. The platelet activating factor (PAF) signaling cascade in systemic inflammatory responses. Biochimie. 2010;92(6):692–7.PubMedCrossRef
34.
go back to reference 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.CrossRef 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.CrossRef
35.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
36.
go back to reference Costa LG, et al. Modulation of paraoxonase (PON1) activity. Biochem Pharmacol. 2005;69(4):541–50.PubMedCrossRef Costa LG, et al. Modulation of paraoxonase (PON1) activity. Biochem Pharmacol. 2005;69(4):541–50.PubMedCrossRef
37.
go back to reference Salvayre R, et al. Oxidized low-density lipoprotein-induced apoptosis. Biochim Biophys Acta. 2002;1585(2–3):213–21.PubMed Salvayre R, et al. Oxidized low-density lipoprotein-induced apoptosis. Biochim Biophys Acta. 2002;1585(2–3):213–21.PubMed
Metadata
Title
High-Density Lipoprotein and Atherosclerosis: The Role of Antioxidant Activity
Authors
Salman Bandeali
John Farmer
Publication date
01-04-2012
Publisher
Current Science Inc.
Published in
Current Atherosclerosis Reports / Issue 2/2012
Print ISSN: 1523-3804
Electronic ISSN: 1534-6242
DOI
https://doi.org/10.1007/s11883-012-0235-2

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