Implications of torcetrapib failure for the future of HDL therapy: Is HDL-cholesterol the right target?

Expert Review of Cardiovascular Therapy

Volumn 8, Issue 3, 2010, Pages 345-358

  Von Eckardstein, Arnold ^a  

^a UNIVERSITY HOSPITAL ZURICH   (Switzerland)

Author keywords

Apolipoprotein A I; Apolipoprotein A I mimetics; Atherosclerosis; ATP binding cassette transporter A1; Biomarkers; Cholesteryl ester transfer protein; Dysfunctional HDL; Metabolic syndrome; Nicotinic acid; Reverse cholesterol transport; Sphingosine 1 phosphate

Indexed keywords

2 METHYLPROPANETHIOIC ACID S [2 [1 (2 ETHYLBUTYL)CYCLOHEXYLCARBOXAMIDO]PHENYL] ESTER; ABC TRANSPORTER A1; ANACETRAPIB; APOLIPOPROTEIN A1; ATORVASTATIN; CHOLESTEROL ESTER TRANSFER PROTEIN; CHOLESTEROL ESTER TRANSFER PROTEIN INHIBITOR; DALCETRAPIB; HIGH DENSITY LIPOPROTEIN CHOLESTEROL; LIVER X RECEPTOR AGONIST; TORCETRAPIB; UNCLASSIFIED DRUG;

ATHEROSCLEROSIS; CARDIOVASCULAR DISEASE; CARDIOVASCULAR RISK; CHOLESTEROL METABOLISM; CHOLESTEROL TRANSPORT; CLINICAL TRIAL; CORONARY ARTERY ATHEROSCLEROSIS; DRUG TARGETING; DYSLIPIDEMIA; GENE FUNCTION; GENE OVEREXPRESSION; GENETIC POLYMORPHISM; HUMAN; HYPERTENSION; LIFESTYLE MODIFICATION; NONHUMAN; PARTICLE SIZE; PROTEIN INTERACTION; REVIEW; RISK REDUCTION;

ANTICHOLESTEREMIC AGENTS; CARDIOVASCULAR DISEASES; CHOLESTEROL, HDL; DRUG DELIVERY SYSTEMS; FEMALE; FOLLOW-UP STUDIES; HUMANS; HYPERCHOLESTEROLEMIA; MALE; QUINOLINES; RISK ASSESSMENT; TREATMENT FAILURE;

EID: 77949458545     PISSN: 14779072     EISSN: 17448344     Source Type: Journal    
DOI: 10.1586/erc.10.6     Document Type: Review

References (123)

1. Cannon CP, Steinberg BA, Murphy SA, Mega JL, Braunwald E. Meta-analysis of cardiovascular outcomes trials comparing intensive versus moderate statin therapy. J. Am. Coll. Cardiol. 48(3), 438-445 (2006).
2. Baigent C, Keech A, Kearney PM et al.; Cholesterol Treatment Trialists' (CTT) collaborators. Efficacy and safety of cholesterol-lowering treatment: prospective meta-analysis of data from 90,056 participants in 14 randomised trials of statins. Lancet 366, 1267-1278 (2005).
3. Nissen SE, Nicholls SJ, Sipahi I et al.; ASTEROID investigators. Effect of very high-intensity statin therapy on regression of coronary atherosclerosis: the ASTEROID trial. JAMA 295(13), 1556-1565 (2006).
4. Smith SC Jr, Allen J, Blair SN et al.; AHA/ACC; National Heart, Lung, and Blood Institute. AHA/ACC guidelines for secondary prevention for patients with coronary and other atherosclerotic vascular disease: update: endorsed by the National Heart, Lung, and Blood Institute. Circulation 113(19), 2363-2372 (2006).
5. Cooney MT, Dudina A, De Bacquer D et al. HDL cholesterol protects against cardiovascular disease in both genders, at all ages and at all levels of risk. Atherosclerosis 206(2), 611-616 (2009).
6. Karthikeyan G, Teo KK, Islam S et al. Lipid profile, plasma Apolipoproteins, and risk of a first myocardial infarction among Asians: an analysis from the INTERHEART Study. J. Am. Coll. Cardiol. 53(3), 244-253 (2009).
7. Lewington S, Whitlock G, Clarke R et al.; Prospective Studies collaboration. Blood cholesterol and vascular mortality by age, sex, and blood pressure: a meta-analysis of individual data from 61 prospective studies with 55,000 vascular deaths. Lancet 370, 1829-1839 (2007).
8. Bolibar I, Von Eckardstein A, Assmann G, Thompson S; on behalf of the ECAT Angina Pectoris study group. Short-term prognostic value of lipid measurements for coronary events in patients with angina pectoris. Thromb. Haemost. 84, 955-960 (2000).
9. Barter P, Gotto AM, LaRosa JC et al.; Treating to New Targets investigators. HDL-cholesterol, very low levels of LDL-cholesterol, and cardiovascular events. N. Engl. J. Med. 357(13), 1301-1310 (2007).
10. De Goma EM, Leeper NJ, Heidenreich PA. Clinical significance of high-density lipoprotein cholesterol in patients with low low-density lipoprotein cholesterol. J. Am. Coll. Cardiol. 51(1), 49-55 (2008).
11. Movva R, Rader DJ. Laboratory assessment of HDL heterogeneity and function. Clin. Chem. 54(5), 788-800 (2008).
12. Von Eckardstein A, Nofer JR, Assmann G. HDL and coronary heart disease: role of cholesterol efflux and reverse cholesterol transport Arterioscler. Thromb. Vasc. Biol. 20, 13-27 (2001).
13. Nofer JR, Kehrel B, Fobker M, Levkau B, Assmann G, Von Eckardstein A. HDL and arteriosclerosis: beyond reverse cholesterol transport. Atherosclerosis 161(1), 1-16 (2002).
14. Tall AR, Yvan-Charvet L, Terasaka N, Pagler T, Wang N. HDL, ABC transporters, and cholesterol efflux: implications for the treatment of Atherosclerosis Cell Metab. 7(5), 365-375 (2008).
15. Linsel-Nitschke P, Tall AR. HDL as a target in the treatment of atherosclerotic cardiovascular disease. Nat. Rev. Drug Discov. 4(3), 193-205 (2005).
16. Joy T, Hegele RA. Is raising HDL a futile strategy for atheroprotection? Nat. Rev. Drug Discov. 7(2), 143-155 (2008).
17. Singh IM, Shishehbor MH, Ansell BJ. High-density lipoprotein as a therapeutic target: a systematic review. JAMA 298(7), 786-798 (2007).
18. Davidsson P, Hulthe J, Fagerberg B, Camejo G. Proteomics of apolipoproteins and associated proteins from plasma high-density lipoproteins. Arterioscler. Thromb. Vasc. Biol. 30(2), 156-163 (2009).
19. Wiesner P, Leidl K, Boettcher A, Schmitz G, Liebisch G. Lipid profiling of FPLC-separated lipoprotein fractions by electrospray ionization tandem mass spectrometry. J. Lipid Res. 50(3), 574-585 (2009).
20. Inazu A, Brown ML, Hesler CB et al. Increased high-density lipoprotein levels caused by a common cholesteryl-ester transfer protein gene mutation. N. Engl. J. Med. 323(18), 1234-1238 (1990).
21. Brousseau ME, Schaefer EJ, Wolfe ML et al. Effects of an inhibitor of cholesteryl ester transfer protein on HDL-cholesterol. N. Engl. J. Med. 350(15), 1505-1515 (2004).
22. Barter PJ, Caulfield M, Eriksson M et al.; ILLUMINATE investigators. Effects of torcetrapib in patients at high risk for coronary events. N. Engl. J. Med. 357(21), 2109-2122 (2007).
23. Kastelein JJ, Van Leuven SI, Burgess L et al.; RADIANCE 1 investigators. Effect of torcetrapib on carotid atherosclerosis in familial hypercholesterolemia. N. Engl. J. Med. 356(16), 1620-1630 (2007).
24. Nissen SE, Tardif JC, Nicholls SJ et al.; ILLUSTRATE investigators. Effect of torcetrapib on the progression of coronary atherosclerosis. N. Engl. J. Med. 356(13), 1304-1316 (2007).
25. Hu X, Dietz JD, Xia C et al. Torcetrapib induces aldosterone and cortisol production by an intracellular calcium-mediated mechanism independently of cholesteryl ester transfer protein inhibition. Endocrinology 150(5), 2211-2219 (2004).
26. Nicholls SJ, Tuzcu EM, Brennan DM, Tardif JC, Nissen SE. Cholesteryl ester transfer protein inhibition, high-density lipoprotein raising, and progression of coronary atherosclerosis: insights from ILLUSTRATE (Investigation of Lipid Level Management Using Coronary Ultrasound to Assess Reduction of Atherosclerosis by CETP Inhibition and HDL Elevation). Circulation 118(24), 2506-2514 (2008).
27. Vergeer M, Bots ML, Van Leuven SI et al. Cholesteryl ester transfer protein inhibitor torcetrapib and off-target toxicity: a pooled analysis of the rating atherosclerotic disease change by imaging with a new CETP inhibitor (RADIANCE) trials. Circulation 118(24), 2515-2522 (2008).
28. Krishna R, Anderson MS, Bergman AJ et al. Effect of the cholesteryl ester transfer protein inhibitor, anacetrapib, on lipoproteins in patients with dyslipidaemia and on 24-h ambulatory blood pressure in healthy individuals: two double-blind, randomised placebo-controlled Phase I studies. Lancet 370(9603), 1907-1914 (2007).
29. Stein EA, Stroes ES, Steiner G et al. Safety and tolerability of dalcetrapib. Am. J. Cardiol. 104(1), 82-91 (2009).
30. Okamoto H, Yonemori F, Wakitani K, Minowa T, Maeda K, Shinkai H. A cholesteryl ester transfer protein inhibitor attenuates atherosclerosis in rabbits. Nature 406(6792), 203-207 (2000).
31. Huang Z, Inazu A, Nohara A, Higashikata T, Mabuchi H. Cholesterylester transfer protein inhibitor (JTT-705) and the development of atherosclerosis in rabbits with severe hypercholesterolaemia. Clin. Sci. (Lond.) 103(6), 587-594 (2002).
32. Zhong S, Sharp DS, Grove JS et al. Increased coronary heart disease in Japanese-American men with mutation in the cholesteryl ester transfer protein gene despite increased HDL levels. J. Clin. Invest. 97(12), 2917-2923 (1996).
33. Curb JD, Abbott RD, Rodriguez BL et al. A prospective study of HDL-C and cholesteryl ester transfer protein gene mutations and the risk of coronary heart disease in the elderly. J. Lipid Res. 45(5), 948-953 (2004).
34. Hirano K, Yamashita S, Kuga Y et al. Atherosclerotic disease in marked hyperalphalipoproteinemia. Combined reduction of cholesteryl ester transfer protein and hepatic triglyceride lipase. Arterioscler. Thromb. Vasc. Biol. 15(11), 1849-1856 (1995).
35. Holleboom AG, Vergeer M, Hovingh GK, Kastelein JJ, Kuivenhoven JA. The value of HDL genetics. Curr. Opin. Lipidol. 19, 385-394 (2008).
36. Thompson A, Di Angelantonio E, Sarwar N et al. Association of cholesteryl ester transfer protein genotypes with CETP mass and activity, lipid levels, and coronary risk. JAMA 299(23), 2777-2788 (2008).
37. Barzilai N, Atzmon G, Schechter C et al. Unique lipoprotein phenotype and genotype associated with exceptional longevity. JAMA 290(15), 2030-2040 (2003).
38. Agerholm-Larsen B, Nordestgaard BG, Steffensen R, Jensen G, Tybjaerg-Hansen A. Elevated HDL-cholesterol is a risk factor for ischemic heart disease in white women when caused by a common mutation in the cholesteryl ester transfer protein gene. Circulation 101(16), 1907-1912 (2000).
39. Bruce C, Sharp DS, Tall AR. Relationship of HDL and coronary heart disease to a common amino acid polymorphism in the cholesteryl ester transfer protein in men with and without hypertriglyceridemia. J. Lipid Res. 39(5), 1071-1078 (1998).
40. Van Acker BA, Botma GJ, Zwinderman AH et al.; REGRESS study group. High HDL cholesterol does not protect against coronary artery disease when associated with combined cholesteryl ester transfer protein and hepatic lipase gene variants. Atherosclerosis 200(1), 161-167 (2008).
41. Regieli JJ, Jukema JW, Grobbee DE et al. CETP genotype predicts increased mortality in statin-treated men with proven cardiovascular disease: an adverse pharmacogenetic interaction. Eur. Heart J. 29(22), 2792-2799 (2008).
42. Zeller M, Masson D, Farnier M et al. High serum cholesteryl ester transfer rates and small high-density lipoproteins are associated with young age in patients with acute myocardial infarction. J. Am. Coll. Cardiol. 50(20), 1948-1955.
43. Klerkx AH, De Grooth GJ, Zwinderman AH, Jukema JW, Kuivenhoven JA, Kastelein JJ. Cholesteryl ester transfer protein concentration is associated with progression of atherosclerosis and response to pravastatin in men with coronary artery disease (REGRESS). Eur J. Clin. Invest. 34(1), 21-28 (2004).
44. De Grooth GJ, Smilde TJ, Van Wissen S et al. The relationship between cholesteryl ester transfer protein levels and risk factor profile in patients with familial hypercholesterolemia. Atherosclerosis 173(2), 261-267 (2004).
45. De Vries-Van Der Weij J, Zadelaar S, Toet K, Havekes LM, Kooistra T, Rensen PC. Human CETP aggravates atherosclerosis by increasing VLDL-cholesterol rather than by decreasing HDL-cholesterol in APOE*3-Leiden mice. Atherosclerosis 206(1), 153-158 (2009).
46. Plump AS, Masucci-Magoulas L, Bruce C, Bisgaier CL, Breslow JL, Tall AR. 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. 19(4), 1105-1110 (1999).
47. Föger B, Chase M, Amar MJ et al. Cholesteryl ester transfer protein corrects dysfunctional high density lipoproteins and reduces aortic atherosclerosis in lecithin cholesterol acyltransferase transgenic mice. J. Biol. Chem. 274(52), 36912-36920 (1999).
48. Hayek T, Masucci-Magoulas L, Jiang X et al. Decreased early atherosclerotic lesions in hypertriglyceridemic mice expressing cholesteryl ester transfer protein transgene. J. Clin. Invest. 96(4), 2071-2074 (1995).
49. Dullaart RP, Dallinga-Thie GM, Wolffenbuttel BH, Van Tol A. CETP inhibition in cardiovascular risk management: a critical appraisal. Eur. J. Clin. Invest. 37(2), 90-98 (2007)
50. erratum in: Eur. J. Clin. Invest. 37(5), 434 (2007).
51. Brousseau ME, Diffenderfer MR, Millar JS et al. Effects of cholesteryl ester transfer protein inhibition on high-density lipoprotein subspecies, Apolipoprotein A-I metabolism, and fecal sterol excretion. Arterioscler. Thromb. Vasc. Biol. 25(5), 1057-1064 (2005).
52. Yvan-Charvet L, Matsuura F, Wang N et al. Inhibition of cholesteryl ester transfer protein by torcetrapib modestly increases macrophage cholesterol efflux to HDL. Arterioscler. Thromb. Vasc. Biol. 27(5), 1132-1138 (2007).
53. Hermann F, Enseleit F, Spieker LE et al. Cholesterylestertransfer protein inhibition and endothelial function in type II hyperlipidemia. Thromb. Res. 123(3), 460-465 (2009).
54. Assmann G, Schulte H, Von Eckardstein A, Huang Y. High-density lipoprotein cholesterol as a predictor of coronary heart disease risk. The PROCAM experience and pathophysiological implications for reverse cholesterol transport. Atherosclerosis 124(Suppl.), S11-S20 (1996).
55. Von Eckardstein A. HDL - a difficult friend. Drug Discov. Today Dis. Mech. 5, e305-e324 (2008).
56. Di Angelantonio E, Sarwar N, Perry P et al.; Emerging Risk Factors collaboration. Major lipids, Apolipoproteins, and risk of vascular disease. JAMA 302(18), 1993-2000 (2009).
57. Nordestgaard BG, Benn M, Schnohr P, Tybjaerg-Hansen A. Nonfasting triglycerides and risk of myocardial infarction, ischemic heart disease, and death in men and women. JAMA 298(3), 299-308 (2007).
58. Bansal S, Buring JE, Rifai N, Mora S, Sacks FM, Ridker PM. Fasting compared with nonfasting triglycerides and risk of cardiovascular events in women. JAMA 298(3), 309-316 (2007).
59. Zilversmit DB. Atherogenesis: a postprandial phenomenon. Circulation 60(3), 473-485 (1979).
60. Von Eckardstein A. Differential diagnosis of familial high density lipoprotein deficiency syndromes. Atherosclerosis 186, 231-239 (2006).
61. Van Dam MJ, De Groot E, Clee SM et al. Association between increased arterial-wall thickness and impairment in ABCA1- driven cholesterol efflux: an observational study. Lancet 359(9300), 37-42 (2002).
62. Hovingh GK, Brownlie A, Bisoendial RJ et al. A novel ApoA-I mutation (L178P) leads to endothelial dysfunction, increased arterial wall thickness, and premature coronary artery disease. J. Am. Coll. Cardiol. 44(7), 1429-1435 (2004).
63. Frikke-Schmidt R, Nordestgaard BG, Stene MC et al. Association of loss-of-function mutations in the ABCA1 gene with high-density lipoprotein cholesterol levels and risk of ischemic heart disease. JAMA 299(21), 2524-2532 (2008).
64. Hegele RA. Plasma lipoproteins: genetic influences and clinical implications. Nat. Rev. Genet. 10(2), 109-121 (2009).
65. Briel M, Ferreira-Gonzalez I, You JJ et al. Association between change in high density lipoprotein cholesterol and cardiovascular disease morbidity and mortality: systematic review and meta-regression analysis. Br. Med. J. 338, b92 (2009).
66. Rimm EB, Williams P, Fosher K, Criqui M, Stampfer MJ. Moderate alcohol intake and lower risk of coronary heart disease: meta-analysis of effects on lipids and haemostatic factors. Br. Med. J. 319(7224), 1523-1528 (1999).
67. Rossouw JE, Cushman M, Greenland P et al. Inflammatory, lipid, thrombotic, and genetic markers of coronary heart disease risk in the women's health initiative trials of hormone therapy. Arch. Intern. Med. 168(20), 2245-2253 (2008).
68. Nissen SE, Tsunoda T, Tuzcu EM et al. Effect of recombinant ApoA-I Milano on coronary atherosclerosis in patients with acute coronary syndromes: a randomized controlled trial. JAMA 290, 2292-2300 (2003).
69. Tardif JC, Grégoire J, L'Allier PL et al.; Effect of rHDL on Atherosclerosis-Safety and Efficacy (ERASE) investigators. Effects of reconstituted high-density lipoprotein infusions on coronary atherosclerosis: a randomized controlled trial. JAMA 297(15), 1675-1682 (2007).
70. Moore RE, Navab M, Millar JS et al. Increased atherosclerosis in mice lacking apolipoprotein A-I attributable to both impaired reverse cholesterol transport and increased inflammation. Circ. Res. 97(8), 763-771 (2005).
71. Li H, Reddick RL, Maeda N. Lack of ApoA-I is not associated with increased susceptibility to atherosclerosis in mice. Arterioscler. Thromb. 13(12), 1814-1821 (1993).
72. Rader DJ. Molecular regulation of HDL metabolism and function: implications for novel therapies. J. Clin. Invest. 116(12), 3090-3100 (2006).
73. Out R, Jessup W, Le Goff W, Hoekstra M et al. Coexistence of foam cells and hypocholesterolemia in mice lacking the ABC transporters A1 and G1. Circ. Res. 102(1), 113-120 (2008).
74. Yvan-Charvet L, Ranalletta M, Wang N et al. Combined deficiency of ABCA1 and ABCG1 promotes foam cell accumulation and accelerates atherosclerosis in mice. J. Clin. Invest. 117(12), 3900-3908 (2007).
75. Out R, Hoekstra M, Habets K et al. Combined deletion of macrophage ABCA1 and ABCG1 leads to massive lipid accumulation in tissue macrophages and distinct atherosclerosis at relatively low plasma cholesterol levels. Arterioscler. Thromb. Vasc. Biol. 28(2), 258-264 (2008).
76. Joyce CW, Amar MJ, Lambert G et al. The ATP binding cassette transporter A1 (ABCA1) modulates the development of aortic atherosclerosis in C57BL/6 and ApoE-knockout mice. Proc. Natl Acad. Sci. USA 99(1), 407-412 (2002).
77. Joyce CW, Wagner EM, Basso F et al. ABCA1 overexpression in the liver of LDLr-KO mice leads to accumulation of pro-atherogenic lipoproteins and enhanced Atherosclerosis J. Biol. Chem. 281(44), 33053-33065 (2006).
78. Brunham LR, Singaraja RR, Duong M et al. Tissue-specific roles of ABCA1 influence susceptibility to atherosclerosis. Arterioscler. Thromb. Vasc. Biol. 29(4), 548-554 (2009).
79. Van Eck M, Singaraja RR, Ye D et al. Macrophage ATP-binding cassette transporter A1 overexpression inhibits atherosclerotic lesion progression in low-density lipoprotein receptor knockout mice. Arterioscler. Thromb. Vasc. Biol. 26(4), 929-934 (2006).
80. Von Eckardstein A, Assmann G. Prevention of coronary heart disease by raising of HDL cholesterol? Curr. Opin. Lipidol. 11, 627-637 (2000).
81. Corsetti JP, Zareba W, Moss AJ, Rainwater DL, Sparks CE. Elevated HDL is a risk factor for recurrent coronary events in a subgroup of non-diabetic postinfarction patients with hypercholesterolemia and inflammation. Atherosclerosis 187(1), 191-197 (2006).
82. Jeppesen J, Hein HO, Suadicani P, Gyntelberg F. Triglyceride concentration and ischemic heart disease: an eight-year follow-up in the Copenhagen Male Study. Circulation 97(11), 1029-1036 (1998).
83. Von Eckardstein A, Schulte H, Assmann G. Increased risk of myocardial infarction in men with both hypertriglyceridemia and elevated HDL cholesterol. Circulation 99(14), 1925 (1999).
84. Canner PL, Berge KG, Wenger NK et al. Fifteen year mortality in Coronary Drug Project patients: long-term benefit with niacin. J. Am. Coll. Cardiol. 8, 1245-1255 (1986).
85. Brown BG, Zhao XQ, Chait A et al. Simvastatin and niacin, antioxidant vitamins, or the combination for the prevention of coronary disease. N. Engl. J. Med. 345(22), 1583-1592 (2001).
86. Taylor AJ, Villines TC, Stanek EJ et al. Extended-release niacin or ezetimibe and carotid intima-media thickness. N. Engl. J. Med. 361(22), 2113-2122 (2009).
87. Barter PJ, Rye KA. Is there a role for fibrates in the management of dyslipidemia in the metabolic syndrome? Arterioscler. Thromb. Vasc. Biol. 28(1), 39-46 (2008).
88. Warden CH, Hedrick CC, Qiao JH, Castellani LW, Lusis AJ. Atherosclerosis in transgenic mice overexpressing Apolipoprotein A-II. Science 261(5120), 469-472 (1993).
89. Braun A, Trigatti BL, Post MJ et al. 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(3), 270-276 (2002).
90. Groen AK, Bloks VW, Bandsma RH, Ottenhoff R, Chimini G, Kuipers F. Hepatobiliary cholesterol transport is not impaired in ABCA1-null mice lacking HDL. J. Clin. Invest. 108(6), 843-850 (2001).
91. Dietschy JM, Turley SD. Control of cholesterol turnover in the mouse. J. Biol. Chem. 277(6), 3801-3804 (2002).
92. Rader DJ, Alexander ET, Weibel GL, Billheimer J, Rothblat GH. The role of reverse cholesterol transport in animals and humans and relationship to atherosclerosis J. Lipid Res. 50(Suppl.), S189-S194 (2009).
93. Timmins JM, Lee JY, Boudyguina E et al. Targeted inactivation of hepatic ABCA1 causes profound hypoalphalipoproteinemia and kidney hypercatabolism of ApoA-I. J. Clin. Invest. 115(5), 1333-1342 (2005).
94. Brunham LR, Kruit JK, Iqbal J et al. Intestinal ABCA1 directly contributes to HDL biogenesis in vivo. J. Clin. Invest. 116(4), 1052-1062 (2006).
95. Cui Y, Watson DJ, Girman CJ et al. Effects of increasing high-density lipoprotein cholesterol and decreasing low-density lipoprotein cholesterol on the incidence of first acute coronary events (from the Air Force/Texas Coronary Atherosclerosis Prevention study). Am. J. Cardiol. 104(6), 829-834 (2009).
96. Kastelein JJ, Van Der Steeg WA, Holme I et al.; TNT Study Group; IDEAL Study Group. Lipids, Apolipoproteins, and their ratios in relation to cardiovascular events with statin treatment. Circulation 117(23), 3002-3009 (2009).
97. Stampfer MJ, Sacks FM, Salvini S, Willett WC, Hennekens CH. A prospective study of cholesterol, Apolipoproteins, and the risk of myocardial infarction. N. Engl. J. Med. 325(6), 373-381 (1991).
98. Luc G, Bard JM, Ferrières J et al. Value of HDL cholesterol, Apolipoprotein A-I, lipoprotein A-I, and lipoprotein A-I/A-II in prediction of coronary heart disease: the PRIME Study. Prospective Epidemiological Study of Myocardial Infarction. Arterioscler. Thromb. Vasc. Biol. 22(7), 1155-1161 (2002).
99. Ala-Korpela M. Critical evaluation of 1H NMR metabonomics of serum as a methodology for disease risk assessment and diagnostics. Clin. Chem. Lab. Med. 46(1), 27-42 (2008).
100. El Harchaoui K, Arsenault BJ, Franssen R et al. High-density lipoprotein particle size and concentration and coronary risk. Ann. Intern. Med. 150(2), 84-93 (2009).
101. Argraves KM, Argraves WS. HDL serves as a S1P signaling platform mediating a multitude of cardiovascular effects. J. Lipid Res. 48(11), 2325-2333 (2007).
102. Vaisar T, Pennathur S, Green PS et al. Shotgun proteomics implicates protease inhibition and complement activation in the antiinflammatory properties of HDL. J. Clin. Invest. 117, 746-756 (2007).
103. Davidson WS, Silva RA, Chantepie S, Lagor WR, Chapman MJ, Kontush A. Proteomic analysis of defined HDL subpopulations reveals particle-specific protein clusters: relevance to antioxidative function. Arterioscler. Thromb. Vasc. Biol. 29(6), 870-876 (2009).
104. Burkard I, Von Eckardstein A, Waeber G, Vollenweider P, Rentsch KM. Lipoprotein distribution and biological variation of 24S- and 27-hydroxycholesterol in healthy volunteers. Atherosclerosis 194(1), 71-78 (2007).
105. Smith JD. Dysfunctional HDL as a diagnostic and therapeutic target. Arterioscler. Thromb. Vasc. Biol. 30(2), 151-155 (2009).
106. Ansell BJ, Fonarow GC, Fogelman AM. The paradox of dysfunctional high-density lipoprotein. Curr. Opin. Lipidol. 18(4), 427-434 (2007).
107. Undurti A, Huang Y, Lupica JA, Smith JD, DiDonato JA, Hazen SL. Modification of high density lipoprotein by myeloperoxidase generates a pro-inflammatory particle. J. Biol. Chem. 284(45), 30825-30835 (2009).
108. Watanabe J, Grijalva V, Hama S et al. Hemoglobin and its scavenger protein haptoglobin associate with ApoA-1- containing particles and influence the inflammatory properties and function of high density lipoprotein. J. Biol. Chem. 284(27), 18292-18301 (2009).
109. Charles-Schoeman C, Watanabe J, Lee YY et al. Abnormal function of high-density lipoprotein is associated with poor disease control and an altered protein cargo in rheumatoid arthritis. Arthritis Rheum. 60(10), 2870-2879 (2009).
110. Duell PB, Oram JF, Bierman EL. Nonenzymatic glycosylation of HDL and impaired HDL-receptor-mediated cholesterol efflux. Diabetes 40(3), 377-384 (1991).
111. Gowri MS, Van Der Westhuyzen DR, Bridges SR, Anderson JW. Decreased protection by HDL from poorly controlled Type 2 diabetic subjects against LDL oxidation may be due to the abnormal composition of HDL. Arterioscler. Thromb. Vasc. Biol. 19(9), 2226-2233 (1999).
112. Sorrentino AS, Besler C, Rohrer L et al. HDL loses beneficial endothelial effects in patients with type-2 diabetes: impact of extended-release niacin therapy. Circulation (2009) (In press).
113. Wong NC. Coronary artery disease - Eighth International Congress. From prevention to intervention. Drugs 12(12), 742-746 (2009).
114. Teupser D, Kretzschmar D, Tennert C et al. Effect of macrophage overexpression of murine liver X receptor-a (LXR- a) on atherosclerosis in LDL-receptor-deficient mice. Arterioscler. Thromb. Vasc. Biol. 28(11), 2009-2015 (2008).
115. Sacks FM, Rudel LL, Conner A et al. Selective delipidation of plasma HDL enhances reverse cholesterol transport in vivo. J. Lipid Res. 50(5), 894-907 (2009).
116. Navab M, Anantharamaiah GM, Reddy ST, Fogelman AM. Apolipoprotein A-I mimetic peptides and their role in atherosclerosis prevention. Nat. Clin. Pract. Cardiovasc. Med. 3(10), 540-547 (2006).
117. Keul P, Tölle M, Lucke S et al. The sphingosine-1-phosphate analogue FTY720 reduces atherosclerosis in Apolipoprotein E-deficient mice. Arterioscler. Thromb. Vasc. Biol. 27(3), 607-613 (2007).
118. Nofer JR, Bot M, Brodde M et al. FTY720, a synthetic sphingosine 1 phosphate analogue, inhibits development of atherosclerosis in low-density lipoprotein receptor-deficient mice. Circulation 115(4), 501-508 (2007).
119. Rohrer L, Hersberger M, Von Eckardstein A. High density lipoproteins in the intersection of diabetes mellitus, inflammation and cardiovascular disease. Curr. Opin. Lipidol. 15(3), 269-278 (2004).
120. Han R, Lai R, Ding Q et al. Apolipoprotein A-I stimulates AMP-activated protein kinase and improves glucose metabolism. Diabetologia 50(9), 1960-1968 (2007).
121. Roehrich ME, Mooser V, Lenain V et al. Insulin-secreting b-cell dysfunction induced by human lipoproteins. J. Biol. Chem. 278(20), 18368-18375 (2003).
122. Brunham LR, Kruit JK, Pape TD et al. b-cell ABCA1 influences insulin secretion, glucose homeostasis and response to thiazolidinedione treatment. Nat. Med. 13(3), 340-347 (2007).
123. Rütti S, Ehses JA, Sibler RA et al. Low- and high-density lipoproteins modulate function, Apoptosis, and proliferation of primary human and murine pancreatic beta-cells. Endocrinology 150(10), 4521-4530 (2009).