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Modulation of High-Density Lipoprotein Cholesterol Metabolism and Reverse Cholesterol Transport

  • Chapter
Atherosclerosis: Diet and Drugs

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 170))

Abstract

Low high-density lipoprotein (HDL)-cholesterol (C) is an important risk factor for coronary heart disease. In vitro, HDL exerts several potentially anti-atherogenic effects including reverse cholesterol transport (RCT) from peripheral cells to the liver. Hence, raising HDL-C has become an interesting target for anti-atherosclerotic drug therapy. Levels of HDL-C and the composition of HDL subclasses in plasma are regulated by apolipoproteins, lipolytic enzymes, lipid transfer proteins, receptors, and cellular transporters. The interplay of these factors leads to RCT and determines the composition and thereby the anti-atherogenic properties of HDL. Recent findings suggest that the mechanism of HDL modification rather than a sole increase in HDL-C determines the efficacy of anti-atherosclerotic drug therapy. In several controlled and prospective intervention studies, patients with low HDL-C and additional risk factors benefited from treatment with fibrates or statins. However, in only some of the fibrate trials was prevention of coronary events in patients with low HDL-C and hypertriglyceridaemia related to an increase in HDL-C. This may be because currently available drugs increase HDL-C levels only moderately and because HDL levels per se do not necessarily correlate with the functionality of HDL. However, several novel targets to modify RCT have emerged from the recent understanding of HDL synthesis, maturation and catabolism. The four major targets for an anti-atherogenic strategy in HDL metabolism include stimulation of apoA-I synthesis and secretion, the stimulation of ABCA1 expression, the inhibition of cholesterol ester transfer protein, and the up-regulation of scavenger receptor BI. These and other modulations of HDL metabolism are thought to result in improved RCT making them attractive targets for the development of new regimens of anti-atherogenic drug therapy.

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References

  • 4S (1994) Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S). Lancet 344:1383–1389

    Google Scholar 

  • WOSCOPS (1998) Influence of pravastatin and plasma lipids on clinical events in the West of Scotland Coronary Prevention Study (WOSCOPS). Circulation 97:1440–1445

    Google Scholar 

  • BIP (2000) Secondary prevention by raising HDL cholesterol and reducing triglycerides in patients with coronary artery disease: the Bezafibrate Infarction Prevention (BIP) study. Circulation 102:21–27

    Google Scholar 

  • WHI(2002) Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results From the Women's Health Initiative randomized controlled trial. JAMA 288:321–333

    Google Scholar 

  • Arai T, Wang N, Bezouevski M, Welch C, Tall AR (1999) Decreased atherosclerosis in heterozygous low density lipoprotein receptor-deficient mice expressing the scavenger receptor BI transgene. J Biol Chem 274:2366–2371

    Article  PubMed  Google Scholar 

  • Ballantyne CM, Herd JA, Ferlic LL, Dunn JK, Farmer JA, Jones PH, Schein JR, Gotto AM, Jr. (1999) Influence of low HDL on progression of coronary artery disease and response to fluvastatin therapy. Circulation 99:736–743

    PubMed  Google Scholar 

  • Ballantyne CM, Olsson AG, Cook TJ, Mercuri MF, Pedersen TR, Kjekshus J (2001) Influence of low high-density lipoprotein cholesterol and elevated triglyceride on coronary heart disease events and response to simvastatin therapy in 4S. Circulation 104:3046–3051

    PubMed  Google Scholar 

  • Barter PJ (2002) Hugh sinclair lecture: the regulation and remodelling of HDL by plasma factors. Atheroscler Suppl 3:39–47

    Article  PubMed  Google Scholar 

  • Bhasin S, Woodhouse L, Casaburi R, Singh AB, Bhasin D, Berman N, Chen X, Yarasheski KE, Magliano L, Dzekov C, Dzekov J, Bross R, Phillips J, Sinha-Hikim I, Shen R, Storer TW (2001) Testosterone dose-response relationships in healthy young men. Am J Physiol Endocrinol Metab 281:E1172–E1181

    PubMed  Google Scholar 

  • Binder EF, Williams DB, Schechtman KB, Jeffe DB, Kohrt WM (2001) Effects of hormone replacement therapy on serumlipids in elderly women. a randomized, placebo-controlled trial. Ann Intern Med 134:754–760

    PubMed  Google Scholar 

  • Bjorkhem I, Diczfalusy U (2002) Oxysterols: friends, foes, or just fellow passengers? Arterioscler Thromb Vasc Biol 22:734–742

    Article  PubMed  Google Scholar 

  • Braun A, Trigatti BL, Post MJ, Sato K, Simons M, Edelberg JM, Rosenberg RD, Schrenzel M, Krieger M (2002) Loss of SR-BI expression leads to the early onset of occlusive atherosclerotic coronary artery disease, spontaneous myocardial infarctions, severe cardiac dysfunction, and premature death in apolipoprotein E-deficient mice. Circ Res 90:270–276

    Article  PubMed  Google Scholar 

  • Brousseau ME, Schaefer EJ, Wolfe ML, Bloedon LT, Digenio AG, Clark RW, Mancuso JP, Rader DJ (2004) Effects of an inhibitor of cholesteryl ester transfer protein on HDL cholesterol. N Engl J Med 350:1505–1515

    Article  PubMed  Google Scholar 

  • Canner PL, Berge KG, Wenger NK, Stamler J, Friedman L, Prineas RJ, Friedewald W (1986) Fifteen year mortality in Coronary Drug Project patients: long-term benefit with niacin. J Am Coll Cardiol 8:1245–1255

    PubMed  Google Scholar 

  • Chen W, Sun Y, Welch C, Gorelik A, Leventhal AR, Tabas I, Tall AR (2001) Preferential ATP-binding cassette transporter A1-mediated cholesterol efflux from late endosomes/lysosomes. J Biol Chem 276:43564–43569

    PubMed  Google Scholar 

  • Christensen EI, Birn H (2002) Megalin and cubilin: multifunctional endocytic receptors. Nat Rev Mol Cell Biol 3:256–266

    PubMed  Google Scholar 

  • Chroni A, Liu T, Gorshkova I, Kan HY, Uehara Y, von Eckardstein A, Zannis VI (2003) The central helices of APOA-I can promote ABCA1-mediated lipid efflux: amino acid residues 220-231 of the wild-type APOA-I are required for lipid efflux in vitro and HDL formation in vivo. J Biol Chem 278:6719–6730

    Article  PubMed  Google Scholar 

  • Clark RW, Sutfin TA, Ruggeri RB, Willauer AT, Sugarman ED, Magnus-Aryitey G, Cosgrove PG, Sand TM, Wester RT, Williams JA, Perlman ME, Bamberger MJ (2004) Raising high-density lipoprotein in humans through inhibition of cholesteryl ester transfer protein: an initial multidose study of torcetrapib. Arterioscler Thromb Vasc Biol 24:490–497

    Article  PubMed  Google Scholar 

  • Cohen JC, Vega GL, Grundy SM (1999) Hepatic lipase: new insights from genetic and metabolic studies. Curr Opin Lipidol 10:259–267

    Article  PubMed  Google Scholar 

  • Connor WE (2001) n-3 Fatty acids from fish and fish oil: panacea or nostrum? Am J Clin Nutr 74:415–416

    PubMed  Google Scholar 

  • Cummings SR, Eckert S, Krueger KA, Grady D, Powles TJ, Cauley JA, Norton L, Nickelsen T, Bjarnason NH, Morrow M, Lippman ME, Black D, Glusman JE, Costa A, Jordan VC (1999) The effect of raloxifene on risk of breast cancer in postmenopausal women: results from the MORE randomized trial. Multiple Outcomes of Raloxifene Evaluation. JAMA 281:2189–2197

    Article  PubMed  Google Scholar 

  • Curtiss LK, Boisvert WA (2000) Apolipoprotein E and atherosclerosis. Curr Opin Lipidol 11:243–251

    Article  PubMed  Google Scholar 

  • Dallongeville J, Bauge E, Tailleux A, Peters JM, Gonzalez FJ, Fruchart JC, Staels B (2001) Peroxisome proliferator-activated receptor alpha is not rate-limiting for the lipoprotein-lowering action of fish oil. J Biol Chem 276:4634–4639

    Article  PubMed  Google Scholar 

  • de Grooth GJ, Kuivenhoven JA, Stalenhoef AF, de Graaf J, Zwinderman AH, Posma JL, van Tol A, Kastelein JJ (2002) Efficacy and safety of a novel cholesteryl ester transfer protein inhibitor, JTT-705, in humans: a randomized phase II dose-response study. Circulation 105:2159–2165

    PubMed  Google Scholar 

  • Despres JP (2001) Increasing high-density lipoprotein cholesterol: an update on fenofibrate. Am J Cardiol 88:30N–36N

    PubMed  Google Scholar 

  • Downs JR, Clearfield M, Weis S, Whitney E, Shapiro DR, Beere PA, Langendorfer A, Stein EA, Kruyer W, Gotto AM, Jr. (1998) 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. JAMA 279:1615–1622

    PubMed  Google Scholar 

  • Edwards PA, Kast HR, Anisfeld AM (2002) BAREing it all: the adoption of LXR and FXR and their roles in lipid homeostasis. J Lipid Res 43:2–12

    PubMed  Google Scholar 

  • Elam MB, Hunninghake DB, Davis KB, Garg R, Johnson C, Egan D, Kostis JB, Sheps DS, Brinton EA (2000) Effect of niacin on lipid and lipoprotein levels and glycemic control in patients with diabetes and peripheral arterial disease: the ADMIT study: A randomized trial. Arterial Disease Multiple Intervention Trial. JAMA 284:1263–1270

    Article  PubMed  Google Scholar 

  • Eriksson M, Carlson LA, Miettinen TA, Angelin B (1999) Stimulation of fecal steroid excretion after infusion of recombinant proapolipoprotein A-I. Potential reverse cholesterol transport in humans. Circulation 100:594–598

    PubMed  Google Scholar 

  • Farmer A, Montori V, Dinneen S, Clar C (2001) Fish oil in people with type 2 diabetes mellitus. Cochrane Database Syst Rev CD003205

    Google Scholar 

  • Fletcher SW, Colditz GA (2002) Failure of estrogen plus progestin therapy for prevention. JAMA 288:366–368

    Article  PubMed  Google Scholar 

  • Frick MH, Syvanne M, Nieminen MS, Kauma H, Majahalme S, Virtanen V, Kesaniemi YA, Pasternack A, Taskinen MR (1997) Prevention of the angiographic progression of coronary and vein-graft atherosclerosis by gemfibrozil after coronary bypass surgery in men with low levels of HDL cholesterol. Lopid Coronary Angiography Trial (LOCAT) Study Group. Circulation 96:2137–2143

    PubMed  Google Scholar 

  • Fruchart JC (2001) Peroxisome proliferator-activated receptor-alpha activation and high-density lipoprotein metabolism. Am J Cardiol 88:24N–29N

    Article  PubMed  Google Scholar 

  • Glass CK, Witztum JL (2001) Atherosclerosis. the road ahead. Cell 104:503–516

    Article  PubMed  Google Scholar 

  • Gotto AM, Jr. (2002) Management of dyslipidemia. Am J Med 112Suppl 8A:10S–18S

    PubMed  Google Scholar 

  • Gotto AM, Jr., Whitney E, Stein EA, Shapiro DR, Clearfield M, Weis S, Jou JY, Langendorfer A, Beere PA, Watson DJ, Downs JR, de Cani JS (2000) Relation between baseline and on-treatment lipid parameters and first acute major coronary events in the Air Force/Texas Coronary Atherosclerosis Prevention Study (AFCAPS/TexCAPS). Circulation 101:477–484

    PubMed  Google Scholar 

  • Grady D, Herrington D, Bittner V, Blumenthal R, Davidson M, Hlatky M, Hsia J, Hulley S, Herd A, Khan S, Newby LK, Waters D, Vittinghoff E, Wenger N (2002) Cardiovascular disease outcomes during 6.8 years of hormone therapy: Heart and Estrogen/progestin Replacement Study follow-up (HERS II). JAMA 288:49–57

    PubMed  Google Scholar 

  • Graf GA, Roswell KL, Smart EJ (2001) 17beta-Estradiol promotes the up-regulation of SR-BII in HepG2 cells and in rat livers. J Lipid Res 42:1444–1449

    PubMed  Google Scholar 

  • Harris WS (1996) n-3 fatty acids and lipoproteins: comparison of results from human and animal studies. Lipids 31:243–252

    PubMed  Google Scholar 

  • Hersberger M, von Eckardstein A (2003) Low high-density lipoprotein cholesterol: physiological background, clinical importance and drug treatment. Drugs 63:1907–1945

    PubMed  Google Scholar 

  • Hirano K, Yamashita S, Matsuzawa Y (2000) Pros and cons of inhibiting cholesteryl ester transfer protein. Curr Opin Lipidol 11:589–596

    Article  PubMed  Google Scholar 

  • Huang Z, Inazu A, Nohara A, Higashikata T, Mabuchi H (2002) Cholesteryl ester transfer protein inhibitor (JTT-705) and the development of atherosclerosis in rabbits with severe hypercholesterolaemia. Clin Sci (Lond) 103:587–594

    PubMed  Google Scholar 

  • Hulley S, Grady D, Bush T, Furberg C, Herrington D, Riggs B, Vittinghoff E (1998) Randomized trial of estrogen plus progestin for secondary prevention of coronary heart disease in postmenopausal women. Heart and Estrogen/progestin Replacement Study (HERS) Research Group. JAMA 280:605–613

    Article  PubMed  Google Scholar 

  • Jiang XC, Qin S, Qiao C, Kawano K, Lin M, Skold A, Xiao X, Tall AR (2001) Apolipoprotein B secretion and atherosclerosis are decreased in mice with phospholipid-transfer protein deficiency. Nat Med 7:847–852

    Article  PubMed  Google Scholar 

  • Johnston CC, Jr., Bjarnason NH, Cohen FJ, Shah A, Lindsay R, Mitlak BH, Huster W, Draper MW, Harper KD, Heath H, III, Gennari C, Christiansen C, Arnaud CD, Delmas PD (2000) Long-term effects of raloxifene on bone mineral density, bone turnover, and serum lipid levels in early postmenopausal women: three-year data from 2 double-blind, randomized, placebo-controlled trials. Arch Intern Med 160:3444–3450

    PubMed  Google Scholar 

  • Kamanna VS, Kashyap ML (2000) Mechanism of action of niacin on lipoprotein metabolism. Curr Atheroscler Rep 2:36–46

    PubMed  Google Scholar 

  • Kaul S, Rukshin V, Santos R, Azarbal B, Bisgaier CL, Johansson J, Tsang VT, Chyu KY, Cercek B, Mirocha J, Shah PK (2003) Intramural delivery of recombinant apolipoprotein AIMilano/ phospholipid complex (ETC-216) inhibits in-stent stenosis in porcine coronary arteries. Circulation 107:2551–2554

    Article  PubMed  Google Scholar 

  • Krieger M (1999) Charting the fate of the “good cholesterol”: identification and characterization of the high-density lipoprotein receptor SR-BI. Annu Rev Biochem 68:523–558

    PubMed  Google Scholar 

  • Laffitte BA, Tontonoz P (2002) Orphan nuclear receptors find a home in the arterial wall. Curr Atheroscler Rep 4:213–221

    PubMed  Google Scholar 

  • Langer C, Gansz B, Goepfert C, Engel T, Uehara Y, von Dehn G, Jansen H, Assmann G, von Eckardstein A (2002) Testosterone up-regulates scavenger receptor B1 and stimulates cholesterol efflux from macrophages. Biochem Biophys Res Commun 296:1051–1057

    Article  PubMed  Google Scholar 

  • Liu T, Krieger M, Kan HY, Zannis VI (2002) The effects of mutations in helices 4 and 6 of ApoA-I on scavenger receptor class B type I (SR-BI)-mediated cholesterol efflux suggest that formation of a productive complex between reconstituted high density lipoprotein and SR-BI is required for efficient lipid transport. J Biol Chem 277:21576–21584

    PubMed  Google Scholar 

  • Llera-Moya M, Rothblat GH, Connelly MA, Kellner-Weibel G, Sakr SW, Phillips MC, Williams DL (1999) Scavenger receptor BI (SR-BI) mediates free cholesterol flux independently of HDL tethering to the cell surface. J Lipid Res 40:575–580

    PubMed  Google Scholar 

  • Manninen V, Elo MO, Frick MH, Haapa K, Heinonen OP, Heinsalmi P, Helo P, Huttunen JK, Kaitaniemi P, Koskinen P (1988) Lipid alterations and decline in the incidence of coronary heart disease in the Helsinki Heart Study. JAMA 260:641–651

    PubMed  Google Scholar 

  • Manninen V, Tenkanen L, Koskinen P, Huttunen JK, Manttari M, Heinonen OP, Frick MH (1992) 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 85:37–45

    PubMed  Google Scholar 

  • Manson JE, Hsia J, Johnson KC, Rossouw JE, Assaf AR, Lasser NL, Trevisan M, Black HR, Heckbert SR, Detrano R, Strickland OL, Wong ND, Crouse JR, Stein E, Cushman M (2003) Estrogen plus progestin and the risk of coronary heart disease. N Engl J Med 349:523–534

    Article  PubMed  Google Scholar 

  • Marchioli R, Barzi F, Bomba E, Chieffo C, Di Gregorio D, Di Mascio R, Franzosi MG, Geraci E, Levantesi G, Maggioni AP, Mantini L, Marfisi RM, Mastrogiuseppe G, Mininni N, Nicolosi GL, Santini M, Schweiger C, Tavazzi L, Tognoni G, Tucci C, Valagussa F (2002) Early protection against sudden death by n-3 polyunsaturated fatty acids after myocardial infarction: time-course analysis of the results of the Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico (GISSI)-Prevenzione. Circulation 105:1897–1903

    PubMed  Google Scholar 

  • Martin G, Duez H, Blanquart C, Berezowski V, Poulain P, Fruchart JC, Najib-Fruchart J, Glineur C, Staels B (2001) Statin-induced inhibition of the Rho-signaling pathway activates PPARalpha and induces HDL apoA-I. J Clin Invest 107:1423–1432

    PubMed  Google Scholar 

  • Martinez LO, Jacquet S, Esteve JP, Rolland C, Cabezon E, Champagne E, Pineau T, Georgeaud V, Walker JE, Terce F, Collet X, Perret B, Barbaras R (2003) Ectopic beta-chain of ATP synthase is an apolipoprotein A-I receptor in hepatic HDL endocytosis. Nature 421:75–79

    Article  PubMed  Google Scholar 

  • Nanjee MN, Cooke CJ, Garvin R, Semeria F, Lewis G, Olszewski WL, Miller NE (2001) Intravenous apoA-I/lecithin discs increase pre-beta-HDL concentration in tissue fluid and stimulate reverse cholesterol transport in humans. J Lipid Res 42:1586–1593

    PubMed  Google Scholar 

  • Navab M, Anantharamaiah GM, Hama S, Garber DW, Chaddha M, Hough G, Lallone R, Fogelman AM (2002) Oral administration of an Apo A-I mimetic Peptide synthesized from D-amino acids dramatically reduces atherosclerosis in mice independent of plasma cholesterol. Circulation 105:290–292

    PubMed  Google Scholar 

  • Navab M, Anantharamaiah GM, Reddy ST, Hama S, Hough G, Grijalva VR, Wagner AC, Frank JS, Datta G, Garber D, Fogelman AM (2004) Oral D-4F causes formation of pre-beta high-density lipoprotein and improves high-density lipoprotein-mediated cholesterol efflux and reverse cholesterol transport from macrophages in apolipoprotein E-null mice. Circulation 109:3215–3220

    Article  PubMed  Google Scholar 

  • Neufeld EB, Remaley AT, Demosky SJ, Stonik JA, Cooney AM, Comly M, Dwyer NK, Zhang M, Blanchette-Mackie J, Santamarina-Fojo S, Brewer HB, Jr. (2001) Cellular localization and trafficking of the human ABCA1 transporter. J Biol Chem 276:27584–27590

    Article  PubMed  Google Scholar 

  • Nissen SE, Tsunoda T, Tuzcu EM, Schoenhagen P, Cooper CJ, Yasin M, Eaton GM, Lauer MA, Sheldon WS, Grines CL, Halpern S, Crowe T, Blankenship JC, Kerensky R (2004) Effect of recombinant ApoA-I Milano on coronary atherosclerosis in patients with acute coronary syndromes: a randomized controlled trial. JAMA 290:2292–2300

    Article  Google Scholar 

  • Nofer JR, Kehrel B, Fobker M, Levkau B, Assmann G, von Eckardstein A (2002) HDL and arteriosclerosis: beyond reverse cholesterol transport. Atherosclerosis 161:1–16

    Article  PubMed  Google Scholar 

  • Okamoto H, Yonemori F, Wakitani K, Minowa T, Maeda K, Shinkai H (2000) A cholesteryl ester transfer protein inhibitor attenuates atherosclerosis in rabbits. Nature 406:203–207

    Article  PubMed  Google Scholar 

  • Oliver WR, Jr., Shenk JL, Snaith MR, Russell CS, Plunket KD, Bodkin NL, Lewis MC, Winegar DA, Sznaidman ML, Lambert MH, Xu HE, Sternbach DD, Kliewer SA, Hansen BC, Willson TM (2001) A selective peroxisome proliferator-activated receptor delta agonist promotes reverse cholesterol transport. Proc Natl Acad Sci USA 98:5306–5311

    Article  PubMed  Google Scholar 

  • Oram JF (2002) ATP-binding cassette transporter A1 and cholesterol trafficking. Curr Opin Lipidol 13:373–381

    PubMed  Google Scholar 

  • Ou J, Tu H, Shan B, Luk A, DeBose-Boyd RA, Bashmakov Y, Goldstein JL, Brown MS (2001) Unsaturated fatty acids inhibit transcription of the sterol regulatory element-binding protein-1c (SREBP-1c) gene by antagonizing ligand-dependent activation of the LXR. Proc Natl Acad Sci USA 98:6027–6032

    Article  PubMed  Google Scholar 

  • Rader DJ, Jaye M (2000) Endothelial lipase: a new member of the triglyceride lipase gene family. Curr Opin Lipidol 11:141–147

    PubMed  Google Scholar 

  • Robins SJ, Collins D, Wittes JT, Papademetriou V, Deedwania PC, Schaefer EJ, McNamara JR, Kashyap ML, Hershman JM, Wexler LF, Rubins HB (2001) Relation of gemfibrozil treatment and lipid levels with major coronary events: VA-HIT: a randomized controlled trial. JAMA 285:1585–1591

    PubMed  Google Scholar 

  • Rothblat GH, Llera-Moya M, Atger V, Kellner-Weibel G, Williams DL, Phillips MC (1999) Cell cholesterol efflux: integration of old and new observations provides new insights. J Lipid Res 40:781–796

    PubMed  Google Scholar 

  • Ruotolo G, Ericsson CG, Tettamanti C, Karpe F, Grip L, Svane B, Nilsson J, de Faire U, Hamsten A (1998) Treatment effects on serum lipoprotein lipids, apolipoproteins and low density lipoprotein particle size and relationships of lipoprotein variables to progression of coronary artery disease in the Bezafibrate Coronary Atherosclerosis Intervention Trial (BECAIT). J Am Coll Cardiol 32:1648–1656

    PubMed  Google Scholar 

  • Rye KA, Clay MA, Barter PJ (1999) Remodelling of high density lipoproteins by plasma factors. Atherosclerosis 145:227–238

    PubMed  Google Scholar 

  • Sacks FM, Tonkin AM, Shepherd J, Braunwald E, Cobbe S, Hawkins CM, Keech A, Packard C, Simes J, Byington R, Furberg CD(2000) Effect of pravastatin on coronary disease events in subgroups defined by coronary risk factors: the Prospective Pravastatin Pooling Project. Circulation 102:1893–1900

    PubMed  Google Scholar 

  • Sakai T, Kamanna VS, Kashyap ML (2001) Niacin, but not gemfibrozil, selectively increases LP-AI, a cardioprotective subfraction of HDL, in patients with low HDL cholesterol. Arterioscler Thromb Vasc Biol 21:1783–1789

    PubMed  Google Scholar 

  • Santamarina-Fojo S, Remaley AT, Neufeld EB, Brewer HB, Jr. (2001) Regulation and intracellular trafficking of the ABCA1 transporter. J Lipid Res 42:1339–1345

    PubMed  Google Scholar 

  • Schaefer JR, Schweer H, Ikewaki K, Stracke H, Seyberth HJ, Kaffarnik H, Maisch B, Steinmetz A (1999) Metabolic basis of high density lipoproteins and apolipoprotein A-I increase by HMG-CoA reductase inhibition in healthy subjects and a patient with coronary artery disease. Atherosclerosis 144:177–184

    Article  PubMed  Google Scholar 

  • Schoonjans K, Staels B, Auwerx J (1996) Role of the peroxisome proliferator-activated receptor (PPAR) in mediating the effects of fibrates and fatty acids on gene expression. J Lipid Res 37:907–925

    PubMed  Google Scholar 

  • Shah PK, Nilsson J, Kaul S, Fishbein MC, Ageland H, Hamsten A, Johansson J, Karpe F, Cercek B (1998) Effects of recombinant apolipoprotein A-I(Milano) on aortic atherosclerosis in apolipoprotein E-deficient mice. Circulation 97:780–785

    PubMed  Google Scholar 

  • Shah PK, Yano J, Reyes O, Chyu KY, Kaul S, Bisgaier CL, Drake S, Cercek B (2001) High-dose recombinant apolipoprotein A-I(milano) mobilizes tissue cholesterol and rapidly reduces plaque lipid and macrophage content in apolipoprotein e-deficient mice. Potential implications for acute plaque stabilization. Circulation 103:3047–3050

    PubMed  Google Scholar 

  • Shepherd J, Packard CJ, Patsch JR, Gotto AM, Jr., Taunton OD (1979) Effects of nicotinic acid therapy on plasma high density lipoprotein subfraction distribution and composition and on apolipoprotein A metabolism. J Clin Invest 63:858–867

    PubMed  Google Scholar 

  • Shih DQ, Bussen M, Sehayek E, Ananthanarayanan M, Shneider BL, Suchy FJ, Shefer S, Bollileni JS, Gonzalez FJ, Breslow JL, Stoffel M (2001) Hepatocyte nuclear factor-1alpha is an essential regulator of bile acid and plasma cholesterol metabolism. Nat Genet 27:375–382

    Article  PubMed  Google Scholar 

  • Silver DL, Tall AR (2001) The cellular biology of scavenger receptor class B type I. Curr Opin Lipidol 12:497–504

    PubMed  Google Scholar 

  • Silver DL, Wang N, Xiao X, Tall AR (2001) High density lipoprotein (HDL) particle uptake mediated by scavenger receptor class B type 1 results in selective sorting of HDL cholesterol from protein and polarized cholesterol secretion. J Biol Chem 276:25287–25293

    Article  PubMed  Google Scholar 

  • Spieker LE, Sudano I, Hurlimann D, Lerch PG, Lang MG, Binggeli C, Corti R, Ruschitzka F, Luscher TF, Noll G (2002) High-density lipoprotein restores endothelial function in hypercholesterolemic men. Circulation 105:1399–1402

    Google Scholar 

  • Takahashi Y, Smith JD (1999) Cholesterol efflux to apolipoprotein AI involves endocytosis and resecretion in a calcium-dependent pathway. Proc Natl Acad Sci USA 96:11358–11363

    PubMed  Google Scholar 

  • Tall AR, Jiang X, Luo Y, Silver D (2000) 1999 George Lyman Duff memorial lecture: lipid transfer proteins, HDL metabolism, and atherogenesis. Arterioscler Thromb Vasc Biol 20:1185–1188

    PubMed  Google Scholar 

  • Tavintharan S, Kashyap ML (2001) The benefits of niacin in atherosclerosis. Curr Atheroscler Rep 3:74–82

    PubMed  Google Scholar 

  • Thuren T (2000) Hepatic lipase and HDL metabolism. Curr Opin Lipidol 11:277–283

    Article  PubMed  Google Scholar 

  • Trigatti B, Rigotti A, Krieger M (2000) The role of the high-density lipoprotein receptor SR-BI in cholesterol metabolism. Curr Opin Lipidol 11:123–131

    PubMed  Google Scholar 

  • Van Lenten BJ, Wagner AC, Anantharamaiah GM, Garber DW, Fishbein MC, Adhikary L, Nayak DP, Hama S, Navab M, Fogelman AM (2002) Influenza infection promotes macrophage traffic into arteries of mice that is prevented by D-4F, an apolipoprotein A-I mimetic peptide. Circulation 106:1127–1132

    PubMed  Google Scholar 

  • Vega GL, Grundy SM (1994) Lipoprotein responses to treatment with lovastatin, gemfibrozil, and nicotinic acid in normolipidemic patients with hypoalphalipoproteinemia. Arch Intern Med 154:73–82

    Article  PubMed  Google Scholar 

  • von Eckardstein A, Crook D, Elbers J, Ragoobir J, Ezeh B, Helmond F, Miller N, Dieplinger H, Coelingh Bennink H, Assmann G (2003) Tibolone lowers HDL cholesterol by increasing hepatic lipase activity but does not impair cholesterol efflux. Clin Endocrinol (Oxford) 58:49–58

    Google Scholar 

  • von Eckardstein A (2004) Therapeutic approaches for the modification of high-density lipoproteins. Drug Discovery Today: Therapeutic Strategies 1:177–187

    Article  Google Scholar 

  • von Eckardstein A, Assmann G (2000) Prevention of coronary heart disease by raising high-density lipoprotein cholesterol? Curr Opin Lipidol 11:627–637

    PubMed  Google Scholar 

  • von Eckardstein A, Langer C, Engel T, Schaukal I, Cignarella A, Reinhardt J, Lorkowski S, Li Z, Zhou X, Cullen P, Assmann G (2001a) ATP binding cassette transporter ABCA1 modulates the secretion of apolipoprotein E from human monocyte-derived macrophages. FASEB J 15:1555–1561

    Article  PubMed  Google Scholar 

  • von Eckardstein A, Nofer JR, Assmann G (2001b) High density lipoproteins and arteriosclerosis. Role of cholesterol efflux and reverse cholesterol transport. Arterioscler Thromb Vasc Biol 21:13–27

    PubMed  Google Scholar 

  • von Eckardstein A, Schmiddem K, Hovels A, Gulbahce E, Schuler-Luttmann S, Elbers J, Helmond F, Bennink HJ, Assmann G (2001c) Lowering of HDL cholesterol in postmenopausal women by tibolone is not associated with changes in cholesterol efflux capacity or paraoxonase activity. Atherosclerosis 159:433–439

    Article  PubMed  Google Scholar 

  • von Eckardstein A, Schulte H, Assmann G (2000) Risk for diabetes mellitus in middle-aged Caucasian male participants of the PROCAM study: implications for the definition of impaired fasting glucose by the American Diabetes Association. Prospective Cardiovascular Munster. J Clin Endocrinol Metab 85:3101–3108

    PubMed  Google Scholar 

  • Wang Y, Oram JF (2002) Unsaturated fatty acids inhibit cholesterol efflux from macrophages by increasing degradation of ATP-binding cassette transporter A1. J Biol Chem 277:5692–5697

    Article  PubMed  Google Scholar 

  • Yoshikawa T, Shimano H, Yahagi N, Ide T, Amemiya-Kudo M, Matsuzaka T, Nakakuki M, Tomita S, Okazaki H, Tamura Y, Iizuka Y, Ohashi K, Takahashi A, Sone H, Osuga JJ, Gotoda T, Ishibashi S, Yamada N (2002) Polyunsaturated fatty acids suppress sterol regulatory element-binding protein 1c promoter activity by inhibition of liver X receptor (LXR) binding to LXR response elements. J Biol Chem 277:1705–1711

    Article  PubMed  Google Scholar 

  • Zhou X, Engel T, Goepfert C, Erren M, Assmann G, von Eckardstein A (2002) The ATP binding cassette transporter A1 contributes to the secretion of interleukin 1beta from macrophages but not from monocytes. Biochem Biophys Res Commun 291:598–604

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Institute of Clinical Chemistry, University and University Hospital Zurich, Raemistrasse 100, 8091, Zurich, Switzerland

    M. Hersberger & A. von Eckardstein

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  1. M. Hersberger
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  2. A. von Eckardstein
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  1. Institute of Clinical Chemistry, University Hospital of Zurich, Rämistrasse 100, 8091, Zürich, Switzerland

    Arnold von Eckardstein

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Hersberger, M., von Eckardstein, A. (2005). Modulation of High-Density Lipoprotein Cholesterol Metabolism and Reverse Cholesterol Transport. In: von Eckardstein, A. (eds) Atherosclerosis: Diet and Drugs. Handbook of Experimental Pharmacology, vol 170. Springer, Berlin, Heidelberg. https://doi.org/10.1007/3-540-27661-0_20

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