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High density lipoproteins (HDLs) and atherosclerosis; the unanswered questions

  • Philip Barter
    Correspondence
    Corresponding author
    Affiliations
    Cardiovascular Investigation Unit, Royal Adelaide Hospital, North Terrace, Adelaide, SA 5000, Australia
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  • John Kastelein
    Affiliations
    Academisch Medisch Centrum-GI147, Meibergdreef 9, 1105 AZ Amsterdam Zuidoost, The Netherlands
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  • Alistair Nunn
    Affiliations
    Edelman Health, Haymarket House, 28–29 Haymarket, London SW1Y 4SP, UK
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  • Richard Hobbs
    Affiliations
    The Medical School, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK
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  • Future Forum Editorial Board
    1
  • Author Footnotes
    1 The Future Forum is a group of global experts, gathered by special invitation, to participate in a forum debating current issues concerning the management of vascular disease through symposia and ‘virtually’ on the Future Forum website http://www.thefutureforum.comThe aim of the Future Forum is to enhance the understanding and management of vascular disease through scientific and clinical discussion. The Future Forum is managed by the Editorial Board, which comprises: Philip Barter (Chairman), Jim Shepherd, John Kastelein, Christie Ballantyne, Richard Hobbs, Virgil Brown, Eric Bruckert, Rafael Carmena, Michael Davidson, Jean Davignon, Jean-Charles Fruchart, Antonio Gotto, Jacques Genest, Wilhem Krone, Lawrence Leiter, Anders Olsson, Chris Packard, Rodolfo Paoletti, Yasushio Saito and Andrew Tonkin.

      Abstract

      The concentration of high density lipoprotein-cholesterol (HDL-C) has been found consistently to be a powerful negative predictor of premature coronary heart disease (CHD) in human prospective population studies. There is also circumstantial evidence from human intervention studies and direct evidence from animal intervention studies that HDLs protect against the development of atherosclerosis. HDLs have several documented functions, although the precise mechanism by which they prevent atherosclerosis remains uncertain. Nor is it known whether the cardioprotective properties of HDL are specific to one or more of the many HDL subpopulations that comprise the HDL fraction in human plasma. Several lifestyle and pharmacological interventions have the capacity to raise the level of HDL-C, although it is not known whether all are equally protective. Indeed, despite the large body of information identifying HDLs as potential therapeutic targets for the prevention of atherosclerosis, there remain many unanswered questions that must be addressed as a matter of urgency before embarking wholesale on HDL-C-raising therapies as strategies to prevent CHD. This review summarises what is known and highlights what we still need to know.

      Keywords

      Abbreviations:

      ABCA1, ATP-binding cassette A1 (), Apo, apolipoprotein (), CAD, coronary artery disease (), CETP, cholesteryl ester transfer protein (), CHD, coronary heart disease (), HDL, high density lipoprotein (), HMGCoA, hydroxy methyl glutaryl CoA (), HL, hepatic lipase (), ICAM, intercellular adhesion molecule (), IMT, intima-media thickness (), LCAT, lecithin:cholesterol acyltransferase (), LDL, low density lipoprotein (), LPL, lipoprotein lipase (), MI, myocardial infarction (), PLTP, phospholipid transfer protein (), PPAR, peroxisome proliferator-activated receptor (), sPLA2, secretory phospholipase A2 (), SR-B1, scavenger receptor B1 (), TG, triglyceride (), TGRL, triglyceride-rich lipoprotein (), VCAM, vascular cell adhesion molecule (), VLDL, very low density lipoprotein ()
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      References

        • Gordon D.J.
        • Knoke J.
        • Probstfield J.L.
        • Superko R.
        • Tyroler H.A.
        High-density lipoprotein cholesterol and coronary heart disease in hypercholesterolemic men: the Lipid Research Clinics Coronary Primary Prevention Trial.
        Circulation. 1986; 74: 1217-1225
        • Enger S.C.
        • Hjermann I.
        • Foss O.P.
        • Helgeland A.
        • Holme I.
        • Leren P.
        • et al.
        High density lipoprotein cholesterol and myocardial infarction or sudden coronary death: a prospective case-control study in middle-aged men of the Oslo study.
        Artery. 1979; 5: 170-181
        • Miller N.E.
        • Thelle D.S.
        • Forde O.H.
        • Mjos O.D.
        • The Tromso heart-study
        High-density lipoprotein and coronary heart-disease: a prospective case-control study.
        Lancet. 1977; 1: 965-968
        • Goldbourt U.
        • Medalie J.H.
        High density lipoprotein cholesterol and incidence of coronary heart disease—the Israeli Ischemic Heart Disease Study.
        Am. J. Epidemiol. 1979; 109: 296-308
        • Gordon T.
        • Castelli W.P.
        • Hjortland M.C.
        • Kannel W.B.
        • Dawber T.R.
        High density lipoprotein as a protective factor against coronary heart disease. The Framingham Study.
        Am. J. Med. 1977; 62: 707-714
        • Jacobs Jr, D.R.
        • Mebane I.L.
        • Bangdiwala S.I.
        • Criqui M.H.
        • Tyroler H.A.
        High density lipoprotein cholesterol as a predictor of cardiovascular disease mortality in men and women: the follow-up study of the Lipid Research Clinics Prevalence Study.
        Am. J. Epidemiol. 1990; 131: 32-47
        • Miller M.
        • Seidler A.
        • Kwiterovich P.O.
        • Pearson T.A.
        Long-term predictors of subsequent cardiovascular events with coronary artery disease and ‘desirable’ levels of plasma total cholesterol.
        Circulation. 1992; 86: 1165-1170
        • Pekkanen J.
        • Linn S.
        • Heiss G.
        • Suchindran C.M.
        • Leon A.
        • Rifkind B.M.
        • et al.
        Ten-year mortality from cardiovascular disease in relation to cholesterol level among men with and without preexisting cardiovascular disease.
        New Engl. J. Med. 1990; 322: 1700-1707
        • Pennacchio L.A.
        • Olivier M.
        • Hubacck J.A.
        • Cohen J.C.
        • Cox D.R.
        • Fruchart J.C.
        • et al.
        An apolipoprotein influencing triglycerides in humans and mice revealed by comparative sequencing.
        Science. 2001; 294: 169-173
        • Duchateau P.N.
        • Pullinger C.R.
        • Orellana R.E.
        • Kunitake S.T.
        • Naya-Vigne J.
        • O'Connor P.M.
        • et al.
        Apolipoprotein L, a new human high density lipoprotein apolipoprotein expressed by the pancreas. Identification, cloning, characterization, and plasma distribution of apolipoprotein L.
        J. Biol. Chem. 1997; 272: 25576-25582
        • Cheung M.C.
        • Wolf A.C.
        • Lum K.D.
        • Tollefson J.H.
        • Albers J.J.
        Distribution and localization of lecithin:cholesterol acyltransferase and cholesteryl ester transfer activity in A-I-containing lipoproteins.
        J. Lipid Res. 1986; 27: 1135-1144
        • Francone O.L.
        • Gurakar A.
        • Fielding C.
        Distribution and functions of lecithin:cholesterol acyltransferase and cholesteryl ester transfer protein in plasma lipoproteins. Evidence for a functional unit containing these activities together with apolipoproteins A-I and D that catalyzes the esterification and transfer of cell-derived cholesterol.
        J. Biol. Chem. 1989; 264: 7066-7072
        • Marcel Y.L.
        • McPherson R.
        • Hogue M.
        • Czarnecka H.
        • Zawadzki Z.
        • Wecch P.K.
        • et al.
        Distribution and concentration of cholesteryl ester transfer protein in plasma of normolipemic subjects.
        J. Clin. Invest. 1990; 85: 10-17
        • Pattnaik N.M.
        • Zilversmit D.B.
        Interaction of cholesteryl ester exchange protein with human plasma lipoproteins and phospholipid vesicles.
        J. Biol. Chem. 1979; 254: 2782-2786
        • Tall A.R.
        • Forester L.R.
        • Bongiovanni G.L.
        Facilitation of phosphatidylcholine transfer into high density lipoproteins by an apolipoprotein in the density 1.20–1.26 g/ml fraction of plasma.
        J. Lipid Res. 1983; 24: 277-289
        • Blanche P.J.
        • Gong E.L.
        • Forte T.M.
        • Nichols A.V.
        Characterization of human high-density lipoproteins by gradient gel electrophoresis.
        Biochim. Biophys. Acta. 1981; 665: 408-419
        • Cheung M.C.
        • Albers J.J.
        Distribution of high density lipoprotein particles with different apoprotein composition: particles with A-I and A-II and particles with A-I but no A-II.
        J. Lipid Res. 1982; 23: 747-753
        • Cheung M.C.
        • Albers J.J.
        Characterization of lipoprotein particles isolated by immunoaffinity chromatography. Particles containing A-I and A-II and particles containing A-I but no A-II.
        J. Biol. Chem. 1984; 259: 12201-12209
        • Bckaert E.D.
        • Alaupovic P.
        • Knight-Gibson C.
        • Norum R.A.
        • Laux M.J.
        • Ayrault-Jarrier M.
        Isolation and partial characterization of lipoprotein A-II (LP-A-II) particles of human plasma.
        Biochim. Biophys. Acta. 1992; 1126: 105-113
        • Asztalos B.F.
        • Sloop C.H.
        • Wong L.
        • Roheim P.S.
        Two-dimensional electrophoresis of plasma lipoproteins: recognition of new apo A-I-containing subpopulations.
        Biochim. Biophys. Acta. 1993; 1169: 291-300
        • Huang Y.
        • von Eckardstein A.
        • Wu S.
        • Assmann G.
        Effects of the apolipoprotein E polymorphism on uptake and transfer of cell-derived cholesterol in plasma.
        J. Clin. Invest. 1995; 96: 2693-2701
        • Kunitake S.T.
        • La Sala K.J.
        • Kane J.P.
        Apolipoprotein A-I-containing lipoproteins with pre-beta electrophoretic mobility.
        J. Lipid Res. 1985; 26: 549-555
        • Sparks D.L.
        • Lund-Katz S.
        • Phillips M.C.
        The charge and structural stability of apolipoprotein A-I in discoidal and spherical recombinant high density lipoprotein particles.
        J. Biol. Chem. 1992; 267: 25839-25847
        • Fielding C.J.
        • Fielding P.E.
        Role of an N-ethylmaleimide-sensitive factor in the selective cellular uptake of low-density lipoprotein free cholesterol.
        Biochemistry. 1995; 34: 14237-14244
        • Otvos J.D.
        • Jeyarajah E.J.
        • Bennett D.W.
        • Krauss K.M.
        Development of a proton nuclear magnetic resonance spectroscopic method for determining plasma lipoprotein concentrations and subspecies distributions from a single, rapid measurement.
        Clin. Chem. 1992; 38: 1632-1638
        • Otvos J.D.
        Measurement of lipoprotein subclass profiles by nuclear magnetic resonance spectroscopy.
        in: Wgdkm R.N. Handbook of lipoprotein testing. AACC Press, Washington, DC2000: 609-623
        • Ala-Korpela M.
        • Korhonen A.
        • Keisala J.
        • Horkko S.
        • Korpi P.
        • Ingman L.P.
        • Jokisaari J.
        • Savolainen M.J.
        • Kesaniemi III, Y.A.
        NMR-based absolute quantitation of human lipoproteins and their lipid contents directly from plasma.
        J. Lipid Res. 1994; 35: 2292-2304
        • Lawn R.M.
        • Wade D.P.
        • Garvin M.R.
        • Wang X.
        • Schwartz K.
        • Porter J.G.
        • et al.
        The Tangier disease gene product ABC1 controls the cellular apolipoprotein-mediated lipid removal pathway.
        J. Clin. Invest. 1999; 104: R25-R31
        • Redgrave T.D.
        • Small D.M.
        Quantitation of the transfer of surface phospholipid of chylomicrons to the high density lipoprotein fraction during the catabolism of chylomicrons in the rat.
        J. Clin. Invest. 1979; 64: 162-171
        • Tall A.R.
        • Blum C.B.
        • Forester G.P.
        • Nelson C.A.
        Changes in the distribution and composition of plasma high density lipoproteins after ingestion of fat.
        J. Biol. Chem. 1982; 257: 198-207
        • Johnson W.J.
        • Mahlbag F.H.
        • Rothblat G.H.
        • Phillips M.C.
        Cholesterol transport between cells and high-density lipoproteins.
        Biochim. Biophys. Acta. 1991; 1085: 273-298
        • Jonas A.
        • von Eckardstein A.
        • Kezdy K.E.
        • Steinmetz A.
        • Assmann G.
        Structural and functional properties of reconstituted high density lipoprotein discs prepared with six apolipoprotein A-I variants.
        J. Lipid Res. 1991; 32: 97-106
        • Nichols A.V.
        • Blanche P.J.
        • Gong E.L.
        • Shore V.G.
        • Forte T.M.
        Molecular pathways in the transformation of model discoidal lipoprotein complexes induced by lecithin: cholesterol acyltransferase.
        Biochim. Biophys. Acta. 1985; 834: 285-300
        • Winkler K.E.
        • Marsh J.B.
        Characterization of nascent high density lipoprotein subfractions from perfusates of rat liver.
        J. Lipid Res. 1989; 30: 979-987
        • Barter P.J.
        • Hopkins G.J.
        • Calvert G.D.
        Pathways for the incorporation of esterified cholesterol into very low density and low density lipoproteins in plasma incubated in vitro.
        Biochim. Biophys. Acta. 1982; 713: 136-148
        • Glass C.
        • Pittman R.C.
        • Weinstein D.B.
        • Steinberg D.
        Dissociation of tissue uptake of cholesterol ester from that of apoprotein A-I of rat plasma high density lipoprotein: selective delivery of cholesterol ester to liver, adrenal, and gonad.
        Proc. Natl. Acad. Sci. USA. 1983; 80: 5435-5439
        • Glass C.
        • Pittman R.C.
        • Civen M.
        • Steinberg D.
        Uptake of high-density lipoprotein-associated apoprotein A-I and cholesterol esters by 16 tissues of the rat in vivo and by adrenal cells and hepatocytes in vitro.
        J. Biol. Chem. 1985; 260: 744-750
        • Acton S.
        • Rigotti A.
        • Landschulz K.T.
        • Xu S.
        • Hobbs H.H.
        • Krieger M.
        Identification of scavenger receptor SR-B1 as a high density lipoprotein receptor.
        Science. 1996; 271: 518-520
        • Liang H.Q.
        • Rye K.A.
        • Barter P.J.
        Dissociation of lipid-free apolipoprotein A-I from high density lipoproteins.
        J. Lipid Res. 1994; 35: 1187-1199
        • Liang H.Q.
        • Rye K.A.
        • Barter P.J.
        Cycling of apolipoprotein A-I between lipid-associated and lipid-free pools.
        Biochim. Biophys. Acta. 1995; 1257: 31-37
        • Horowitz B.S.
        • Goldberg I.J.
        • Merab J.
        • Vanni T.M.
        • Ramakrishnan R.
        • Ginsberg H.N.
        Increased plasma and renal clearance of an exchangeable pool of apolipoprotein A-I in subjects with low levels of high density lipoprotein cholesterol.
        J. Clin. Invest. 1993; 91: 1743-1752
        • Rader D.J.
        • Castro G.
        • Zech L.A.
        • Fruchart J.C.
        • Brewer Jr, H.B.
        In vivo metabolism of apolipoprotein A-I on high density lipoprotein particles LpA-I and LpA-I, A-II.
        J. Lipid Res. 1991; 32: 1849-1859
        • Ikewaki K.
        • Zech L.A.
        • Kindt M.
        • Brewer Jr, H.B.
        • Rader D.J.
        Apolipoprotein A-II production rate is a major factor regulating the distribution of apolipoprotein A-I among HDL subclasses LpA-I and LpA-I:A-II in normolipidemic humans.
        Arterioscler. Thromb. Vasc. Biol. 1995; 15: 306-331
        • Rader D.J.
        • Schaefer J.R.
        • Lohse P.
        • Ikewaki K.
        • Thomas F.
        • Harris W.A.
        • Zech L.A.
        • Dujovne C.A.
        • Brewer Jr, H.B.
        Increased production of apolipoprotein A-I associated with elevated plasma levels of high-density lipoproteins, apolipoprotein A-I, and lipoprotein A-I in a patient with familial hyperalphalipoproteinemia.
        Metabolism. 1993; 42: 1429-1434
        • Barter P.J.
        HDL and reverse cholesterol transport.
        Curr. Opin. Lipidol. 1993; 4: 210-217
        • Fielding C.J.
        • Fielding P.E.
        Molecular physiology of reverse cholesterol transport.
        J. Lipid Res. 1995; 36: 211-228
        • Levine D.M.
        • Parker T.S.
        • Donnelly T.M.
        • Walsh A.
        • Rubin A.L.
        In vivo protection against endotoxin by plasma high density lipoprotein.
        Proc. Natl. Acad. Sci. USA. 1993; 90: 12040-12044
        • Murugesan G.
        • Sa G.
        • Fox P.L.
        High-density lipoprotein stimulates endothelial cell movement by a mechanism distinct from basic fibroblast growth factor.
        Circ. Res. 1994; 74: 1149-1156
        • Sugatani J.
        • Miwa M.
        • Komiyama Y.
        • Ito S.
        High-density lipoprotein inhibits the synthesis of platelet-activating factor in human vascular endothelial cells.
        J. Lipid Mediators Cell Signal. 1996; 13: 73-88
        • Epand R.M.
        • Stafford A.
        • Leon B.
        • Lock P.E.
        • Tytler E.M.
        • Segrest J.P.
        • et al.
        HDL and apolipoprotein A-I protect erythrocytes against the generation of procoagulant activity.
        Arterioscler. Thromb. 1994; 14: 1775-1783
        • Fleisher L.N.
        • Tall A.R.
        • Witte L.U.
        • Miller R.W.
        • Cannon P.J.
        Stimulation of arterial endothelial cell prostacyclin synthesis by high density lipoproteins.
        J. Biol. Chem. 1982; 257: 6653-6655
        • Tamagaki T.
        • Sawada S.
        • Imamura H.
        • Tada Y.
        • Yamasaki S.
        • Toratani A.
        • et al.
        Effects of high-density lipoproteins on intracellular pH and proliferation of human vascular endothelial cells.
        Atherosclerosis. 1996; 123: 73-82
        • Yui Y.
        • Aoyama T.
        • Morishita H.
        • Takahashi M.
        • Takatsu Y.
        • Kawai C.
        Serum prostacyclin stabilizing factor is identical to apolipoprotein A-I (Apo A-I). A novel function of Apo A-I.
        J. Clin. Invest. 1988; 82: 803-807
        • Zeiher A.M.
        • Schachinger V.
        Coronary endothelial vasodilator dysfunction: clinical relevance and therapeutic implications.
        Z. Kardiol. 1994; 83: 7-14
        • Ko Y.
        • Haring R.
        • Stiebler H.
        • Wieczorek A.J.
        • Vetter H.
        • Sachinidis A.
        High-density lipoprotein reduces epidermal growth factor-induced DNA synthesis in vascular smooth muscle cells.
        Atherosclerosis. 1993; 99: 253-259
        • O'Connell B.J.
        • Genest Jr, J.
        High-density lipoproteins and endothelial function.
        Circulation. 2001; 104: 1978-1983
        • Gordon D.J.
        • Probstfield J.L.
        • Garrison R.J.
        • Neaton J.D.
        • Castelli W.P.
        • Knoke J.D.
        • et al.
        High-density lipoprotein cholesterol and cardiovascular disease. Four prospective American studies.
        Circulation. 1989; 79: 8-15
        • Austin M.A.
        Plasma triglyceride and coronary heart disease.
        Arterioscler. Thromb. 1991; 11: 2-14
        • Austin M.A.
        • Breslow J.L.
        • Hennekens C.H.
        • Buring J.E.
        • Willett W.C.
        • Krauss R.M.
        Low-density lipoprotein subclass patterns and risk of myocardial infarction.
        J. Am. Med. Assoc. 1988; 260: 1917-1921
        • Steiner G.
        • Schwartz L.
        • Shumak S.
        • Poapst M.
        The association of increased levels of intermediate-density lipoproteins with smoking and with coronary artery disease.
        Circulation. 1987; 75: 124-130
        • Reardon M.K.
        • Nestel P.J.
        • Craig I.H.
        • Harper R.W.
        Lipoprotein predictors of the severity of coronary artery disease in men and women.
        Circulation. 1985; 71: 881-888
        • Tatami R.
        • Mabuchi H.
        • Ueda K.
        • Ueda R.
        • Haba T.
        • Kametani T.
        • et al.
        Intermediate-density lipoprotein and cholesterol-rich very low density lipoprotein in angiographically determined coronary artery disease.
        Circulation. 1981; 64: 1174-1184
        • Krauss R.M.
        • Lindgren F.T.
        • Williams P.T.
        • Kelsey S.F.
        • Brensike J.
        • Vranizan K.
        • et al.
        Intermediate-density lipoproteins and progression of coronary artery disease in hypercholesterolaemic men.
        Lancet. 1987; 2: 62-66
        • Despres J.P.
        • Moorjani S.
        • Ferland M.
        • Tremblay A.
        • Lupien P.J.
        • Nadeau A.
        • et al.
        Adipose tissue distribution and plasma lipoprotein levels in obese women. Importance of infra-abdominal fat.
        Arteriosclerosis. 1989; 9: 203-210
        • Haffner S.M.
        • Valdez R.A.
        • Hazuda H.P.
        • Mitchell B.D.
        • Morales P.A.
        • Stern M.P.
        Prospective analysis of the insulin-resistance syndrome (syndrome X).
        Diabetes. 1992; 41: 715-722
        • Sirtori C.R.
        • Calabresi L.
        • Franceschini G.
        • Baldassarre D.
        • Amato M.
        • Johansson J.
        • et al.
        Cardiovascular status of carriers of the apolipoprotein A-I (Milano) mutant: the Limone sul Garda study.
        Circulation. 2001; 103: 1949-1954
        • Berge K.G.
        • Canner P.L.
        Coronary drug project: experience with niacin. Coronary drug project research group.
        Eur. J. Clin. Pharmacol. 1991; 40: S49-S51
      1. Lipid Research Clinic Program. The lipid research clinics coronary primary prevention trial results. 1. Reduction in incidence of coronary heart disease, J. Am. Med. Assoc. 1984;251:351–64.

        • Shepherd J.
        • Cobbe S.M.
        • Ford I.
        • Isles C.G.
        • Lorimer A.R.
        • Macfarlane P.W.
        • et al.
        Prevention of coronary heart disease with pravastatin in men with hypercholesterolemia. West of Scotland coronary prevention study group.
        New Engl. J. Med. 1995; 333: 1301-1307
        • Downs J.R.
        • Clearfield M.
        • Weis S.
        • Whitney E.
        • Shapiro D.R.
        • Beere P.A.
        • et al.
        Primary prevention of acute coronary events with lovastatin in men and women with average cholesterol levels: results of AFCAPS/TexCAPS. Air Force/Texas coronary atherosclerosis prevention study.
        J. Am. Med. Assoc. 1998; 279: 1615-1622
      2. The Scandinavian Simvastatin Survival Group. Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian simvastatin survival study (4S), Lancet 1994;344:1383–9.

        • Sacks F.M.
        • Pfeffer M.A.
        • Moye L.A.
        • Rouleau J.L.
        • Rutherford J.D.
        • Cole T.G.
        • et al.
        The effect of pravastatin on coronary events after myocardial infarction in patients with average cholesterol levels. Cholesterol and recurrent events trial investigators.
        New Engl. J. Med. 1996; 335: 1001-1009
        • The Long-term Intervention with Pravastatin in Ischacmic Disease (LIPTD) Study Group
        Prevention of cardiovascular events and death with pravastatin in patients with coronary heart disease and a broad range of initial cholesterol levels.
        New Engl. J. Med. 1998; 339: 1349-1357
        • Heart Protection Study Collaborative Group
        MRC/BHF Heart protection study of cholesterol lowering with simvastatin in 20 536 high-risk individuals: a randomised placebo-controlled trial.
        Lancet. 2002; 360: 7-22
        • Frick M.H.
        • Elo O.
        • Haapa K.
        • Hcinonen O.P.
        • Heinsalmi P.
        • Helo P.
        • et al.
        Helsinki heart study: primary-prevention trial with gemfibrozil in middle-aged men with dyslipidemia. Safety of treatment, changes in risk factors, and incidence of coronary heart disease.
        New Engl. J. Med. 1987; 317: 1237-1245
        • Manninen V.
        • Tenkanen L.
        • Koskinen P.
        • Huttunen J.K.
        • Manttari M.
        • Heinonen O.P.
        • et al.
        Joint effects of serum triglyceride and LDL cholesterol and HDL cholesterol concentrations on coronary heart disease risk in the Helsinki heart study. Implications for treatment.
        Circulation. 1992; 85: 37-45
        • Rubins H.B.
        • Robins S.J.
        • Collins D.
        • Fye C.L.
        • Anderson J.W.
        • Elam M.B.
        • et al.
        Gemfibrozil for the secondary prevention of coronary heart disease in men with low levels of high-density lipoprotein cholesterol. Veterans affairs high-density lipoprotein cholesterol intervention trial study group.
        New Engl. J. Med. 1999; 341: 410-418
        • Robins S.J.
        • Collins D.
        • Wittes J.T.
        • Papademetriou V.
        • Deedwania P.C.
        • Schaetbr E.J.
        • et al.
        Relation of gemfibrozil treatment and lipid levels with major coronary events: VA-HIT: a randomized controlled trial.
        J. Am. Med. Assoc. 2001; 285: 1585-1591
      3. The BIP Study Group. Secondary prevention by raising HDL cholesterol and reducing triglycerides in patients with coronary artery disease: the bezafibrate infarction prevention (BIP) study, Circulation 2000;102:21–27.

        • Badimon J.J.
        • Badimon L.
        • Fuster V.
        Regression of atherosclerotic lesions by high density lipoprotein plasma traction in the cholesterol-fed rabbit.
        J. Clin. Invest. 1990; 85: 1234-1241
        • Chiesa G.
        • Monteggia R.
        • Marchesi M.
        • Lorenzon P.
        • Laucello M.
        • Lorusso V.
        • et al.
        Recombinant apolipoprotein A-I Milano infusion into rabbit carotid artery rapidly removes lipid from fatty streaks.
        Circ. Res. 2002; 90: 974-980
        • Duverger M.
        • Knith H.
        • Emmanuel F.
        • Caillaud J.M.
        • Viglietta C.
        • Castro G.
        • et al.
        Inhibition of atherosclerosis development in cholesterol-fed human apolipoprotein A-I-transgenic rabbits.
        Circulation. 1996; 94: 713-717
        • Rubin E.M.
        • Krauss R.M.
        • Spangler E.A.
        • Veratuyft J.G.
        • Clitt S.M.
        Inhibition of early atherogenesis in transgenic mice by human apolipoprotein AI.
        Nature. 1991; 353: 265-267
        • Plump A.S.
        • Scott C.J.
        • Breslow J.L.
        Human apolipoprotein A-I gene expression increases high density lipoprotein and suppresses atherosclerosis in the apolipoprotein H-deficient mouse.
        Proc. Natl. Acad. Sci. USA. 1994; 91: 9607-9611
        • Tangirala R.K.
        • Tsukamoto K.
        • Chun S.H.
        • Usher D.
        • Pure K.
        • Rader D.J.
        Regression of atherosclerosis induced by liver-directed gene transfer of apolipoprotein A-I in mice.
        Circulation. 1999; 100: 1816-1822
        • Liu A.C.
        • Lawn R.M.
        • Verstuyft J.G.
        • Rubin E.M.
        Human apolipoprotein A-I prevents atherosclerosis associated with apolipoprotein[a] in transgenic mice.
        J. Lipid Res. 1994; 35: 2263-2267
        • Schultz J.R.
        • Verstuyft J.G.
        • Gong E.L.
        • Nichols A.V.
        • Rubin E.M.
        Protein composition determines the anti-atherogenic properties of HDL in transgenic mice.
        Nature. 1993; 365: 762-764
        • Tailleux A.
        • Bouly M.
        • Luc G.
        • Castro G.
        • Caillaud J.M.
        • Hennuyer N.
        • et al.
        Decreased susceptibility to diet-induced atherosclerosis in human apolipoprotein A-II transgenic mice.
        Arterioscler. Thromb. Vasc. Biol. 2000; 20: 2453-2458
        • Warden C.H.
        • Hcdrick C.C.
        • Qiao J.H.
        • Castellani L.W.
        • Lusis A.J.
        Atherosclerosis in transgenic mice overexpressing apolipoprotein A-II.
        Science. 1993; 261: 469-472
        • Li H.
        • Reddick R.L.
        • Maeda N.
        Lack of apoA-I is not associated with increased susceptibility to atherosclerosis in mice.
        Arterioscler. Thromb. 1993; 13: 1814-1821
        • Charo I.F.
        Monocyte–endothelial cell interactions.
        Curr. Opin. Lipidol. 1992; 3: 335-343
        • Steinberg D.
        • Parthasarathy S.
        • Carew T.F.
        • Khoo J.C.
        • Witztum J.L.
        Beyond cholesterol. Modifications of low-density lipoprotein that increase its atherogenicity.
        New Engl. J. Med. 1989; 320: 915-924
        • Navab M.
        • Imes S.S.
        • Hama S.Y.
        • Hough G.P.
        • Ross L.A.
        • Bork R.W.
        • et al.
        Monocyte transmigration induced by modification of low density lipoprotein in cocultures of human aortic wall cells is due to induction of monocyte chemotactic protein 1 synthesis and is abolished by high density lipoprotein.
        J. Clin. Invest. 1991; 88: 2039-2046
        • Ross R.
        The pathogenesis of atherosclerosis: a perspective for the 1990s.
        Nature. 1993; 362: 801-809
        • Nathan C.F.
        Secretory products of macrophages.
        J. Clin. Invest. 1987; 79: 319-326
        • Springer T.A.
        Adhesion receptors of the immune system.
        Nature. 1990; 346: 425-434
        • Ross R.
        • Agius L.
        The process of atherogenesis—cellular and molecular interaction: from experimental animal models to humans.
        Diabetologia. 1992; 35: S34-S40
        • Clee S.M.
        • Kastelein J.J.
        • van Dam M.
        • Marcil M.
        • Roomp K.
        • Zwarts K.Y.
        • et al.
        Age and residual cholesterol efflux affect HDL cholesterol levels and coronary artery disease in ABCA1 heterozygotes.
        J. Clin. Invest. 2000; 106: 1263-1270
        • Attie A.D.
        • Kastelein J.P.
        • Hayden M.R.
        Pivotal role of ABCA1 in reverse cholesterol transport influencing HDL levels and susceptibility to atherosclerosis.
        J. Lipid Res. 2001; 42: 1717-1726
        • Aiello R.J.
        • Brecs D.
        • Liourassa P.-A.
        • Royer L.
        • Lindsey S.
        • et al.
        Increased atherosclerosis in hyperlipidemic mice with inactivation of ABCA1 in macrophages.
        Arterioscler. Thromb. Vasc. Biol. 2002; 22: 630-637
        • Hessler J.R.
        • Robertson Jr, A.L.
        • Chisolm III, G.M.
        LDL-induced cytotoxicity and its inhibition by HDL in human vascular smooth muscle and endothelial cells in culture.
        Atherosclerosis. 1979; 32: 213-229
        • Sue I.
        • Escargueil-Blane I.
        • Troly M.
        • Salvayre R.
        • Negre-Salvayre A.
        HDL and ApoA prevent cell death of endothelial cells induced by oxidized LDL.
        Arterioscler. Thromb. Vasc. Biol. 1997; 17: 2158-2166
        • Maier J.A.
        • Barenghi L.
        • Bradamante S.
        • Pagani F.
        Modulators of oxidized LDL-induced hyperadhesiveness in human endothelial cells.
        Biochem. Biophys. Res. Commun. 1994; 204: 673-677
        • Decossin C.
        • Tailleux A.
        • Fruchart J.C.
        • Fievet C.
        Prevention of in vitro low-density lipoprotein oxidation by an albumin-containing Lp A-I subfraction.
        Biochim. Biophys. Acta. 1995; 1255: 31-38
        • Kunilake S.T.
        • Jarvis M.R.
        • Hamilton R.L.
        • Kane J.P.
        Binding of transition metals by apolipoprotein A-I-containing plasma lipoproteins; inhibition of oxidation of low density lipoproteins.
        Proc. Natl. Acad. Sci. USA. 1992; 89: 6993-6997
        • Ohta T.
        • Takata K.
        • Horiuchi S.
        • Morino Y.
        • Matsuda I.
        Protective effect of lipoproteins containing apoprotein A-I on Cu2+-catalyzed oxidation of human low density lipoprotein.
        FEES Lett. 1989; 257: 435-438
        • Mackness M.I.
        • Abbott C.
        • Arrol S.
        • Durrington P.N.
        The role of high-density lipoprotein and lipid-soluble antioxidant vitamins in inhibiting low-density lipoprotein oxidation.
        Biochem. J. 1993; 294: 829-834
        • Mackness M.I.
        • Durrington P.N.
        HDL, its enzymes and its potential to influence lipid peroxidation.
        Atherosclerosis. 1995; 115: 243-253
        • Parthasarathy S.
        • Barnett J.
        • Fong L.G.
        High-density lipoprotein inhibits the oxidative modification of low-density lipoprotein.
        Biochim. Biophys. Acta. 1990; 1044: 275-283
        • Klimov A.N.
        • Gurevich V.S.
        • Nikiforova A.A.
        • Shatilina L.V.
        • Kuzmin A.A.
        • Plavinsky S.L.
        • et al.
        Antioxidative activity of high density lipoproteins in vivo.
        Atherosclerosis. 1993; 100: 13-18
        • Mackness M.I.
        • Arrol S.
        • Abbott C.
        • Durrington P.N.
        Protection of low-density lipoprotein against oxidative modification by high-density lipoprotein associated paraoxonase.
        Atherosclerosis. 1993; 104: 129-135
        • Mackness M.I.
        • Arrol S.
        • Durrington P.N.
        Paraoxonase prevents accumulation of lipoperoxides in low-density lipoprotein.
        FEES Lett. 1991; 286: 152-154
        • Watson A.D.
        • Berliner J.A.
        • Hama S.Y.
        • La Du B.N.
        • Faull K.F.
        • Fogelman A.M.
        • et al.
        Protective effect of high density lipoprotein associated paraoxonase. Inhibition of the biological activity of minimally oxidized low density lipoprotein.
        J. Clin. Invest. 1995; 96: 2882-2891
        • Garner B.
        • Waldeek A.R.
        • Witting P.K.
        • Rye K.A.
        • Stocker R.
        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: 6088-6095
        • Cockerill G.W.
        • Rye K.A.
        • Gamble J.R.
        • Vadas M.A.
        • Barter P.J.
        High-density lipoproteins inhibit cytokine-induced expression of endothelial cell adhesion molecules.
        Arterioscler. Thromb. Vasc. Biol. 1995; 15: 1987-1994
        • Xia P.
        • Vadas M.A.
        • Rye K.A.
        • Barter P.J.
        • Gamble J.R.
        High density lipoproteins (HDL) interrupt the sphingosine kinase signaling pathway. A possible mechanism for protection against atherosclerosis by HDL.
        J. Biol. Chem. 1999; 274: 33143-33147
        • Baker P.W.
        • Rye K.A.
        • Gamble J.R.
        • Vadas M.A.
        • Barter P.J.
        Phospholipid composition of reconstituted high density lipoproteins influences their ability to inhibit endothelial cell adhesion molecule expression.
        J. Lipid Res. 2000; 41: 1261-1267
        • Calabresi L.
        • Gomaraschi M.
        • Villa B.
        • Omoboni L.
        • Dmitrieff C.
        • et al.
        Elevated soluble cellular adhesion molecules in subjects with low HDL-cholesterol.
        Arterioscler. Thromb. Vasc. Biol. 2002; 22: 656-661
        • Yuhanna I.S.
        • Zhu Y.
        • Cox B.E.
        • Hahner L.D.
        • Osborne-Lawrence S.
        • Lu P.
        • et al.
        High-density lipoprotein binding to scavenger receptor-BI activates endothelial nitric oxide synthase.
        Nat. Med. 2001; 7: 853-857
        • Spieker L.E.
        • Sudano I.
        • Hurlimann D.
        • Lerch P.G.
        • Lang M.G.
        • et al.
        High-density lipoprotein restores endothelial function in hypercholesterolemic men.
        Circulation. 2002; 105: 1399-1402
        • Amouyel P.
        • Isorez D.
        • Bard J.M.
        • Goldman M.
        • Lebel P.
        • Zylberberg G.
        • et al.
        Parental history of early myocardial infarction is associated with decreased levels of lipoparticle AI in adolescents.
        Arterioscler. Thromb. 1993; 13: 1640-1644
        • Tailleux A.
        • Bouly M.
        • Luc G.
        • et al.
        Decreased susceptibility to diet-induced atherosclerosis in human apolipoprotein A-II transgenic mice.
        Arterioscler. Thromb. Vasc. Biol. 2000; 20: 2453-2458
        • Miller N.E.
        Associations of high-density lipoprotein subclasses and apolipoproteins with ischemic heart disease and coronary atherosclerosis.
        Am. Heart J. 1987; 113: 589-597
        • Castro G.R.
        • Fielding C.J.
        Early incorporation of cell-derived cholesterol into pre-beta-migrating high-density lipoprotein.
        Biochemistry. 1988; 27: 25-29
        • Syvanne M.
        • Nieminen M.S.
        • Frick M.H.
        • Kauma H.
        • Majahalme S.
        • Virtanen V.
        • et al.
        Associations between lipoproteins and the progression of coronary and vein-graft atherosclerosis in a controlled trial with gemfibrozil in men with low baseline levels of HDL cholesterol.
        Circulation. 1998; 98: 1993-1999
        • Brooks-Wilson A.
        • Marcil M.
        • Clee S.M.
        • Zhang L.H.
        • Roomp K.
        • van Dam M.
        • et al.
        Mutations in ABC1 in Tangier disease and familial high-density lipoprotein deficiency.
        Nat. Genet. 1999; 22: 336-345
        • Funke H.
        • von Eckardstein A.
        • Pritchard P.H.
        • Karas M.
        • Albers J.J.
        • Assmann G.
        A frameshift mutation in the human apolipoprotein A-I gene causes high density lipoprotein deficiency, partial lecithin: cholesterol-acyltransferase deficiency, and corneal opacities.
        J. Clin. Invest. 1991; 87: 371-376
        • Lackner K.J.
        • Dieplinger H.
        • Nowicka G.
        • Schmitz G.
        High density lipoprotein deficiency with xanthomas. A defect in reverse cholesterol transport caused by a point mutation in the apolipoprotein A-I gene.
        J. Clin. Invest. 1993; 92: 2262-2273
        • Reymer P.W.
        • Gagne E.
        • Groenemeyer B.E.
        • Zhang H.
        • Forsyth I.
        • Jansen H.
        • et al.
        A lipoprotein lipase mutation (Asn291Scr) is associated with reduced HDL cholesterol levels in premature atherosclerosis.
        Nat. Genet. 1995; 10: 28-34
        • Carlson L.A.
        • Holmquist L.
        Evidence for deficiency of high density lipoprotein lecithin: cholesterol acyltransferase activity (alpha-LCAT) in fish eye disease.
        Acta Med. Scand. 1985; 218: 189-196
        • Funke H.
        • von Eckardstein A.
        • Pritchard P.H.
        • Homby A.E.
        • Wiebusch H.
        • Motti C.
        • et al.
        Genetic and phenotypic heterogeneity in familial lecithin: cholesterol acyltransferase (LCAT) deficiency. Six newly identified detective alleles further contribute to the structural heterogeneity in this disease.
        J. Clin. Invest. 1993; 91: 677-683
        • Klein H.G.
        • Lohse P.
        • Pritchard P.H.
        • Bojanovski D.
        • Schmidt H.
        • Brewer Jr, H.E.
        Two different allelic mutations in the lecithin-cholesterol acyltransferase gene associated with the fish eye syndrome. Lecithin–cholesterol acyltransferase (Thr123–He) and lecithin–cholesterol acyltransferase (Thr347–Met).
        J. Clin. Invest. 1992; 89: 499-506
        • Wiebusch H.
        • Cullen P.
        • Owen J.S.
        • Collins D.
        • Sharp P.S.
        • Funke H.
        • et al.
        Deficiency of lecithin: cholesterol acyltransferase due to compound heterozygosity of two novel mutations (Gly33Arg and 30 bp ins) in the LCAT gene.
        Hum. Mol. Genet. 1995; 4: 143-145
        • Akita H.
        • Chiba H.
        • Tsuchihashi K.
        • Tsuji M.
        • Kumagai M.
        • Matsuno K.
        • et al.
        Cholesteryl ester transfer protein gene: two common mutations and their effect on plasma high-density lipoprotein cholesterol content.
        J. Clin. Endocrinol. Metab. 1994; 79: 1615-1618
        • Bisgaier C.L.
        • Siebenkas M.V.
        • Brown M.L.
        • Inazu A.
        • Koizumi J.
        • Mabuchi H.
        • et al.
        Familial cholesteryl ester transfer protein deficiency is associated with triglyceride-rich low density lipoproteins containing cholesteryl esters of probable intracellular origin.
        J. Lipid Res. 1991; 32: 21-33
        • Inazu A.
        • Brown M.L.
        • Hesler C.B.
        • Agellon L.B.
        • Koizumi J.
        • Takata K.
        • et al.
        Increased high-density lipoprotein levels caused by a common cholesteryl–ester transfer protein gene mutation.
        New Engl. J. Med. 1990; 323: 1234-1238
        • Koizumi J.
        • Inazu A.
        • Yagi K.
        • Koizumi I.
        • Uno Y.
        • Kajinami K.
        • et al.
        Serum lipoprotein lipid concentration and composition in homozygous and heterozygous patients with cholesteryl ester transfer protein deficiency.
        Atherosclerosis. 1991; 90: 189-196
        • Groenemeijer B.E.
        • Hallman M.D.
        • Reymer P.W.
        • Gagne E.
        • Kuivenhoven J.A.
        • Bruin T.
        • et al.
        Genetic variant showing a positive interaction with beta-blocking agents with a beneficial influence on lipoprotein lipase activity, HDL cholesterol, and triglyceride levels in coronary artery disease patients. The Ser447-stop substitution in the lipoprotein lipase gene. REGRESS study group.
        Circulation. 1997; 95: 2628-2635
        • Reddy M.N.
        Effect of anticonvulsant drugs on plasma total cholesterol, high-density lipoprotein cholesterol, and apolipoproteins A and B in children with epilepsym.
        Proc. Soc. Exp. Biol. Med. 1985; 180: 359-363
        • Harris W.S.
        n−3 Fatty acids and serum lipoproteins: human studies.
        Am. J. Clin. Nutr. 1997; 65: 1645S-1654
        • Mensink R.P.
        • Katan M.B.
        Effect of dietary fatty acids on serum lipids and lipoproteins. A meta-analysis of 27 trials.
        Arterioscler. Thromb. 1992; 12: 911-919
        • Hegsted D.M.
        • Ausman L.M.
        • Johnson J.A.
        • Dallal G.E.
        Dietary fat and serum lipids: an evaluation of the experimental data.
        Am. J. Clin. Nutr. 1993; 57: 875-883
        • Yu S.
        • Derr J.
        • Etherton T.D.
        • Kris-Etherton P.M.
        Plasma cholesterol-predictive equations demonstrate that stearic acid is neutral and monounsaturated fatty acids are hypocholesterolemic.
        Am. J. Clin. Nutr. 1995; 61: 1129-1139
        • Howell W.H.
        • McNamara D.J.
        • Tosca M.A.
        • Smith B.T.
        • Gaines J.A.
        Plasma lipid and lipoprotein responses to dietary fat and cholesterol: a meta-analysis.
        Am. J. Clin. Nutr. 1997; 65: 1747-1764
        • Gardner C.D.
        • Kraemer H.C.
        Monounsaturated versus polyunsaturated dietary fat and serum lipids. A meta-analysis.
        Arterioscler. Thromb. Vasc. Biol. 1995; 15: 1917-1927
        • Harris W.S.
        Fish oils and plasma lipid and lipoprotein metabolism in humans: a critical review.
        J. Lipid Res. 1989; 30: 785-807
        • Miettinen T.A.
        • Kesaniemi Y.A.
        Cholesterol absorption: regulation of cholesterol synthesis and elimination and within-population variations of serum cholesterol levels.
        Am. J. Clin. Nutr. 1989; 49: 629-635
        • Ginsberg H.N.
        Nonpharmacologic management of low levels of high-density lipoprotein cholesterol.
        Am. J. Cardiol. 2000; 86: 41L-45L
        • Leon A.S.
        • Connett J.
        Physical activity and 10.5 year mortality in the multiple risk factor intervention trial (MRFIT).
        Int. J. Epidemiol. 1991; 20: 690-697
        • Krummel D.
        • Etherton T.D.
        • Peterson S.
        • Kris-Etherton P.M.
        Effects of exercise on plasma lipids and lipoproteins of women.
        Proc. Soc. Exp. Biol. Med. 1993; 204: 123-137
        • Superko H.R.
        Exercise training, serum lipids, and lipoprotein particles: is there a change threshold.
        Med. Sci. Sports Exerc. 1991; 23: 677-685
        • Durstine J.L.
        • Haskell W.L.
        Effects of exercise training on plasma lipids and lipoproteins.
        Exerc. Sport Sci. Rev. 1994; 22: 477-521
        • Bergeron J.
        • Couillard C.
        • Despres J.P.
        • Gagnon J.
        • Leon A.S.
        • Rao D.C.
        • Skinner J.S.
        • Wilmore J.H.
        • Bouchard C.
        Race differences in the response of postheparin plasma lipoprotein lipase and hepatic lipase activities to endurance exercise training in men: results from the HERITAGE family study.
        Atherosclerosis. 2001; 159: 399-406
        • van Tol A.
        • Hendriks H.P.
        Moderate alcohol consumption: effects on lipids and cardiovascular disease risk.
        Curr. Opin. Lipidol. 2001; 12: 19-23
        • Hannuksela M.
        • Marcel Y.L.
        • Kesaniemi Y.A.
        • Savolainen M.J.
        Reduction in the concentration and activity of plasma cholesteryl ester transfer protein by alcohol.
        J. Lipid Res. 1992; 33: 737-744
        • Freeman D.J.
        • Caslake M.J.
        • Griffin B.A.
        • Hinnie J.
        • Tan C.E.
        • Watson T.D.
        • et al.
        The effect of smoking on post-heparin lipoprotein and hepatic lipase, cholesteryl ester transfer protein and lecithin; cholesterol amyl transferase activities in human plasma.
        Eur. J. Clin. Invest. 1998; 28: 584-591
        • Manttari M.
        • Tenkanen I.-
        • Maenpaa H.
        • Manninen V.
        • Huttunen J.K.
        High-density lipoprotein cholesterol elevation with gemfibrozil: effects of baseline level and modifying factors.
        Clin. Pharmacol. Ther. 1993; 54: 437-447
        • Spencer C.M.
        • Barradell L.B.
        Gemfibrozil. A reappraisal of its pharmacological properties and place in the management of dyslipidaemia.
        Drugs. 1996; 51: 982-1018
        • Fruchart J.-C.
        • Staels B.
        • Duriez P.
        The role of fibric acids in atherosclerosis.
        Curr. Atheroscler. Rep. 2001; 3: 83-92
        • Torra I.P.
        • Chinctti G.
        • Duval C.
        • et al.
        Peroxisome proliferator-activated receptors: from transcriptional control to clinical practice.
        Curr. Opin. Lipidol. 2001; 12: 245-254
        • Staels B.
        • Dallongeville J.
        • Auwerx J.
        • et al.
        Mechanism of action of fibrates on lipid and lipoprotein metabolism.
        Circulation. 1998; 98: 2088-2093
        • Pineda T.I.
        • Gervois P.
        • Staels B.
        Peroxisome proliferator-activated receptor alpha in metabolic disease, inflammation, atherosclerosis and aging.
        Curr. Opin. Lipidol. 1999; 10: 151-159
        • Branchi A.
        • Fiorenza A.M.
        • Torri A.
        • Muzio F.
        • Berra C.
        • Colombo E.
        • et al.
        Effects of low doses of simvastatin and atorvastatin on high-density lipoprotein cholesterol levels in patients with hypercholesterolemia.
        Clin. Ther. 2001; 23: 851-857
        • Jones P.
        • Kafonek S.
        • Laurora I.
        • Hunninghake D.
        Comparative dose efficacy study of atorvastatin versus simvastatin, pravastatin, lovastatin, and fluvastatin in patients with hypercholesterolemia (the CURVES study).
        Am. J. Cardiol. 1998; 81: 582-587
        • Smilde T.J.
        • van Wissen S.
        • Wollersheim H.
        • Trip M.D.
        • Kastelein J.J.
        • Stalenhoef A.K.
        Effect of aggressive versus conventional lipid lowering on atherosclerosis progression in familial hypercholesterolaemia (ASAP): a prospective, randomised, double-blind trial.
        Lancet. 2001; 357: 577-581
      4. Stein EA, Strutt KL, Miller E, Southworth H. Effect of rosuvastatin on high density lipoprotein cholesterol and apolipoprotein A-I in patients with heterozygous familial hypercholesterolaemia, Int. J. Clin. Pract. 2002;56(Supp 124):9.

      5. Olsson AG, Southworth H, Wilpshaar JW. A 52-week trial of rosuvastatin versus atorvastatin in patients with primary hypercholesterolaemia, Int. J. Clin. Pract. 2002;56(Supp 124):11.

        • Martin G.
        • Duez H.
        • Blanquart C.
        • Berezowski V.
        • Poulain P.
        • Fruchart J.C.
        • et al.
        Statin-induced inhibition of the Rho-signaling pathway activates PPARalpha and induces HDL apoA-I.
        J. Clin. Invest. 2001; 107: 1423-1432
        • McPherson R.
        Comparative effects of simvastatin and cholestyramine on plasma lipoproteins and CETP in humans.
        Can. J. Clin. Pharmacol. 1999; 6: 85-90
        • Shepherd J.
        • Packard C.J.
        • Patsch J.R.
        • Gotto Jr, A.M.
        • Taunton O.D.
        Effects of nicotinic acid therapy on plasma high density lipoprotein subtraction distribution and composition and on apolipoprotein A metabolism.
        J. Clin. Invest. 1979; 63: 858-867
        • Wink J.
        • Giacoppe G.
        • King J.
        Effect of very-low-dose niacin on high-density lipoprotein in patients undergoing long-term statin therapy.
        Am. Heart J. 2002; 143: 514-518
        • Barter P.J.
        • Rye K.A.
        Cholesteryl ester transfer protein, high density lipoprotein and arterial disease.
        Curr. Opin. Lipidol. 2001; 12: 377-382
        • Sugano M.
        • Makino N.
        • Sawada S.
        • Otsuka S.
        • Watanabe M.
        • Okamoto H.
        • et al.
        Effect of antisense oligonuelcotides against cholesteryl ester transfer protein on the development of atherosclerosis in cholesterol-fed rabbits.
        J. Biol. Chem. 1998; 273: 5033-5036
        • Rittershaus C.W.
        • Miller D.P.
        • Thomas L.J.
        • Picard M.D.
        • Honan C.M.
        • Rmmett C.D.
        • et al.
        Vaccine-induced antibodies inhibit CETP activity in vivo and reduce aortic lesions in a rabbit model of atherosclerosis.
        Arterioscler. Thromb. Vasc. Biol. 2000; 20: 2106-2112
        • Okamoto H.
        • Yonemori F.
        • Wakitani K.
        • Minowa T.
        • Maeda K.
        • Shinkai H.
        A cholesteryl ester transfer protein inhibitor attenuates atherosclerosis in rabbits.
        Nature. 2000; 406: 203-207
        • Marotti K.R.
        • Castle C.K.
        • Boyle T.P.
        • Lin A.H.
        • Murray R.W.
        • Melchior G.W.
        Severe atherosclerosis in transgenic mice expressing simian cholesteryl ester transfer protein.
        Nature. 1993; 364: 73-75
        • Plump A.S.
        • Masucci-Magoulas L.
        • Bruce C.
        • Bisgaier C.L.
        • Breslow J.L.
        • Tall A.R.
        Increased atherosclerosis in ApoE and LDL receptor gene knock-out mice as a result of human cholesteryl ester transfer protein transgene expression.
        Arterioscler. Thromb. Vasc. Biol. 1999; 19: 1105-1110
        • Foger B.
        • Chase M.
        • Amar M.J.
        • Vaisman B.L.
        • Shamburek R.D.
        • Paigen B.
        • et al.
        Cholesteryl ester transfer protein corrects dysfunctional high density lipoproteins and reduces aortic atherosclerosis in lecithin cholesterol acyltransferase transgenic mice.
        J. Biol. Chem. 1999; 274: 36912-36920
        • Hayek T.
        • Masucci-Magoulas L.
        • Jiang X.
        • Walsh A.
        • Rubin E.
        • Breslow J.L.
        • et al.
        Decreased early atherosclerotic lesions in hypertriglyceridemic mice expressing cholesteryl ester transfer protein transgene.
        J. Clin. Invest. 1995; 96: 2071-2074
        • Moriyama Y.
        • Okamura T.
        • Inazu A.
        • Doi M.
        • Iso H.
        • Mouri Y.
        • et al.
        A low prevalence of coronary heart disease among subjects with increased high-density lipoprotein cholesterol levels, including those with plasma cholesteryl ester transfer protein deficiency.
        Prev. Med. 1998; 27: 659-667
        • Hirano K.
        • Yamashita S.
        • Kuga Y.
        • Sakai N.
        • Nozaki S.
        • Kihara S.
        • et al.
        Atherosclerotic disease in marked hyperalphalipoproteinemia. Combined reduction of cholesteryl ester transfer protein and hepatic triglyceride lipase.
        Arterioscler. Thromb. Vasc. Biol. 1995; 15: 1849-1856
        • de Grooth G.J.
        • Kuivenhoven J.A.
        • Stalemhoef A.F.H.
        • de Graaf J.
        • Zwinderman A.H.
        • et al.
        Efficacy and safety of a novel cholesteryl ester transfer protein inhibitor, JTT-705, in humans. A randomised phase II dose–response study.
        Circulation. 2002; 105: 2159-2165
        • Rye K.A.
        • Clay M.A.
        • Barter P.J.
        Remodelling of high density lipoproteins by plasma factors.
        Atherosclerosis. 1999; 145: 227-238
        • Hoeg J.M.
        • Santamarina-Fojo S.
        • Berard A.M.
        • Cornhill J.F.
        • Herderick E.E.
        • Feldman S.H.
        • et al.
        Overexpression of lecithin:choleaterol acyltransferase in transgenic rabbits prevents diet-induced atherosclerosis.
        Proc. Natl. Acad. Sci. USA. 1996; 93: 11448-11453
        • Berard A.M.
        • Foger B.
        • Remaley A.
        • Shamburek R.
        • Vaisman B.L.
        • Talley G.
        • et al.
        High plasma HDL concentrations associated with enhanced atherosclerosis in transgenic mice overexpressing lecithin-cholestetyl acyltransferase.
        Nat. Med. 1997; 3: 744-749
        • Kuivenhoven J.A.
        • Pritchard H.
        • Hill J.
        • Frohlich J.
        • Assmann G.
        • Kastelein J.
        The molecular pathology of lecithin:choleslero1 acyltransferase (LCAT) deficiency syndromes.
        J. Lipid Res. 1997; 38: 191-205
        • Vaisman B.L.
        • Lambert G.
        • Amar M.
        • Joyce C.
        • Ito T.
        • Shamburek R.D.
        • et al.
        ABCA1 overexpression leads to hyperalphalipoproteinemia and increased biliary cholesterol excretion in transgenic mice.
        J. Clin. Invest. 2001; 108: 303-309
        • Singaraja K.R.
        • Bocher V.
        • James E.R.
        • Clec S.M.
        • Zhang L.H.
        • Leavitt B.R.
        • et al.
        Human ABCA1 BAC transgenic mice show increased high density lipoprotein cholesterol and ApoAI-dependent efflux stimulated by an internal promoter containing liver X receptor response elements in intron 1.
        J. Biol. Chem. 2001; 276: 33969-33979
        • Ueda Y.
        • Gong E.
        • Royer L.
        • Cooper P.N.
        • Francone O.L.
        • Rubin E.M.
        Relationship between expression levels and atherogenesis in scavenger receptor class B, type I transgenics.
        J. Biol. Chem. 2000; 275: 20368-20373