HDL-targeted therapies: Progress, failures and future

Nature Reviews Drug Discovery

Volumn 13, Issue 6, 2014, Pages 445-464

  Kingwell, Bronwyn A ^a   Chapman, M John ^b   Kontush, Anatol ^b   Miller, Norman E ^c  

^a BAKER IDI HEART AND DIABETES INSTITUTE   (Australia)

^b PITIÉ SALPÊTRIÈRE HOSPITAL   (France)

^c MAGDALEN COLLEGE   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

3 [3 [[2 CHLORO 3 (TRIFLUOROMETHYL)BENZYL](2 DIPHENYLETHYL)AMINO]PROPOXY]PHENYLACETIC ACID; ACP 501; AGENTS AFFECTING LIPID METABOLISM; ANACETRAPIB; ANTISENSE OLIGONUCLEOTIDE; APP 018; BEZAFIBRATE; CER 001; CHOLESTEROL ESTER TRANSFER PROTEIN INHIBITOR; CSL 111; CSL 112; DALCETRAPIB; DELIPIDATED HIGH DENSITY LIPOPROTEIN; ETC 216; EVACETRAPIB; EZETIMIBE; FENOFIBRATE; FIBRIC ACID DERIVATIVE; GEMFIBROZIL; HIGH DENSITY LIPOPROTEIN; HIGH DENSITY LIPOPROTEIN CHOLESTEROL; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE INHIBITOR; LAROPIPRANT; LIVER X RECEPTOR AGONIST; MDCO 216; NICOTINIC ACID; PLACEBO; RVX 208; SIMVASTATIN; TORCETRAPIB; UNCLASSIFIED DRUG; UNINDEXED DRUG;

ACUTE CORONARY SYNDROME; AORTA ATHEROSCLEROSIS; ATHEROGENESIS; ATHEROSCLEROSIS; ATHEROSCLEROTIC CARDIOVASCULAR DISEASE; ATHEROSCLEROTIC PLAQUE; CARDIOVASCULAR DISEASE; CARDIOVASCULAR RISK; CORONARY ARTERY ATHEROSCLEROSIS; CORONARY ARTERY DISEASE; DOSE RESPONSE; DRUG DOSE ESCALATION; DRUG MECHANISM; DRUG MEGADOSE; DRUG SAFETY; DRUG WITHDRAWAL; FAMILIAL HYPERCHOLESTEROLEMIA; FLUSHING; GENE MUTATION; HEART INFARCTION; HUMAN; HYPERTENSION; INFLAMMATION; ISCHEMIC HEART DISEASE; LOW DRUG DOSE; MOLECULARLY TARGETED THERAPY; MYOPATHY; NONHUMAN; PATHOPHYSIOLOGY; PRIORITY JOURNAL; REVIEW; SIDE EFFECT; SINGLE DRUG DOSE; SINGLE NUCLEOTIDE POLYMORPHISM; THROMBOSIS;

ANIMALS; APOLIPOPROTEIN A-I; CARDIOVASCULAR DISEASES; CHOLESTEROL ESTER TRANSFER PROTEINS; CLINICAL TRIALS AS TOPIC; DRUGS, INVESTIGATIONAL; HUMANS; HYPOLIPIDEMIC AGENTS; LIPOPROTEINS, HDL; MODELS, BIOLOGICAL; MOLECULAR TARGETED THERAPY; NIACIN; PHOSPHATIDYLCHOLINE-STEROL O-ACYLTRANSFERASE; RECOMBINANT PROTEINS; UP-REGULATION;

EID: 84901924957     PISSN: 14741776     EISSN: 14741784     Source Type: Journal    
DOI: 10.1038/nrd4279     Document Type: Review

References (225)

1. Rosenson, R. S. et al. Cholesterol efflux and atheroprotection: advancing the concept of reverse cholesterol transport. Circulation 125, 1905-1919 (2012).
2. Barr, D. P., Russ, E. M. & Eder, H. A. Protein-lipid relationships in human plasma. II. In atherosclerosis and related conditions. Am. J. Med. 11, 480-493 (1951).
3. Gofman, J. W. Serum lipoproteins and the evaluation of atherosclerosis. Ann. NY Acad. Sci. 64, 590-595 (1956).
4. Gofman, J. W., Malamud, N., Simon, A., Waters, E. S. & Young, W. The interrelationship between cerebral and coronary atherosclerosis; a preliminary report. Geriatrics 11, 413-418 (1956).
5. Miller, G. J. & Miller, N. E. Plasma-high-density-lipoprotein concentration and development of ischaemic heart-disease. Lancet 1, 16-19 (1975).
6. Castelli, W. P. et al. HDL cholesterol and other lipids in coronary heart disease. The cooperative lipoprotein phenotyping study. Circulation 55, 767-772 (1977).
7. Miller, N. E., Thelle, D. S., Forde, O. H. & Mjos, O. D. The Tromsø heart-study. High-density lipoprotein and coronary heart-disease: a prospective case-control study. Lancet 1, 965-968 (1977).
8. 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, S11-S20 (1996).
9. Ishikawa, T., Fidge, N., Thelle, D. S., Forde, O. H. & Miller, N. E. The Tromso Heart Study: serum apolipoprotein AI concentration in relation to future coronary heart disease. Eur. J. Clin. Invest. 8, 179-182 (1978).
10. McQueen, M. J. et al. Lipids, lipoproteins, and apolipoproteins as risk markers of myocardial infarction in 52 countries (the INTERHEART study): a case-control study. Lancet 372, 224-233 (2008).
11. Yusuf, S. et al. Effect of potentially modifiable risk factors associated with myocardial infarction in 52 countries (the INTERHEART study): case-control study. Lancet 364, 937-952 (2004).
12. Kuller, L. H., Grandits, G., Cohen, J. D., Neaton, J. D. & Prineas, R. Lipoprotein particles, insulin, adiponectin, C-reactive protein and risk of coronary heart disease among men with metabolic syndrome. Atherosclerosis 195, 122-128 (2007).
13. Mackey, R. H. et al. High-density lipoprotein cholesterol and particle concentrations, carotid atherosclerosis, and coronary events: MESA (multiethnic study of atherosclerosis). J. Am. Coll. Cardiol. 60, 508-516 (2012).
14. Otvos, J. D. et al. Low-density lipoprotein and high-density lipoprotein particle subclasses predict coronary events and are favorably changed by gemfibrozil therapy in the Veterans Affairs High-Density Lipoprotein Intervention Trial. Circulation 113, 1556-1563 (2006).
15. Parish, S. et al. Lipids and lipoproteins and risk of different vascular events in the MRC/BHF Heart Protection Study. Circulation 125, 2469-2478 (2012).
16. Mora, S., Glynn, R. J. & Ridker, P. M. High-density lipoprotein cholesterol, size, particle number, and residual vascular risk after potent statin therapy. Circulation 128, 1189-1197 (2013).
17. Van Lenten, B. J. et al. Anti-inflammatory HDL becomes pro-inflammatory during the acute phase response. Loss of protective effect of HDL against LDL oxidation in aortic wall cell cocultures. J. Clin. Invest. 96, 2758-2767 (1995).
18. Huang, Y. et al. An abundant dysfunctional apolipoprotein A1 in human atheroma. Nature Med. 20, 193-203 (2014).
19. Rye, K. A. & Barter, P. J. Regulation of high-density lipoprotein metabolism. Circ. Res. 114, 143-156 (2014).
20. Calkin, A. C. et al. Reconstituted high-density lipoprotein attenuates platelet function in individuals with type 2 diabetes mellitus by promoting cholesterol efflux. Circulation 120, 2095-2104 (2009).
21. Murphy, A. J. et al. Cholesterol efflux in megakaryocyte progenitors suppresses platelet production and thrombocytosis. Nature Med. 19, 586-594 (2013).
22. Kontush, A. et al. Preferential sphingosine-1-phosphate enrichment and sphingomyelin depletion are key features of small dense HDL3 particles: relevance to antiapoptotic and antioxidative activities. Arterioscler. Thromb. Vasc. Biol. 27, 1843-1849 (2007).
23. Patel, S. et al. Reconstituted high-density lipoprotein increases plasma high-density lipoprotein anti-inflammatory properties and cholesterol efflux capacity in patients with type 2 diabetes. J. Am. Coll. Cardiol. 53, 962-971 (2009).
24. de Souza, J. A. et al. Small, dense HDL 3 particles attenuate apoptosis in endothelial cells: pivotal role of apolipoprotein A-I. J. Cell. Mol. Med. 14, 608-620 (2010).
25. Bisoendial, R. J. et al. Restoration of endothelial function by increasing high-density lipoprotein in subjects with isolated low high-density lipoprotein. Circulation 107, 2944-2948 (2003).
26. Nieuwdorp, M. et al. Reconstituted HDL infusion restores endothelial function in patients with type 2 diabetes mellitus. Diabetologia 51, 1081-1084 (2008).
27. Spieker, L. E. et al. High-density lipoprotein restores endothelial function in hypercholesterolemic men. Circulation 105, 1399-1402 (2002).
28. Besler, C. et al. Mechanisms underlying adverse effects of HDL on eNOS-activating pathways in patients with coronary artery disease. J. Clin. Invest. 121, 2693-2708 (2011).
29. Barter, P. J. et al. Effect of torcetrapib on glucose, insulin, and hemoglobin A1c in subjects in the Investigation of Lipid Level Management to Understand its Impact in Atherosclerotic Events (ILLUMINATE) trial. Circulation 124, 555-562 (2011).
30. Drew, B. G. et al. High-density lipoprotein modulates glucose metabolism in patients with type 2 diabetes mellitus. Circulation 119, 2103-2111 (2009).
31. Drew, B. G., Rye, K. A., Duffy, S. J., Barter, P. & Kingwell, B. A. The emerging role of HDL in glucose metabolism. Nature Rev. Endocrinol. 8, 237-245 (2012).
32. Fryirs, M. A. et al. Effects of high-density lipoproteins on pancreatic β-cell insulin secretion. Arterioscler. Thromb. Vasc. Biol. 30, 1642-1648 (2010).
33. Kontush, A. & Chapman, M. J. High-density lipoproteins: Structure, Metabolism, Function and Therapeutics (John Wiley and Sons, 2012).
34. Reiner, Z. et al. ESC/EAS Guidelines for the management of dyslipidaemias: the task force for the management of dyslipidaemias of the European Society of Cardiology (ESC) and the European Atherosclerosis Society (EAS). Eur. Heart J. 32, 1769-1818 (2011).
35. Assmann, G., Schulte, H., Cullen, P. & Seedorf, U. Assessing risk of myocardial infarction and stroke: new data from the Prospective Cardiovascular Munster (PROCAM) study. Eur. J. Clin. Invest. 37, 925-932 (2007).
36. D'Agostino, R. B. Sr et al. General cardiovascular risk profile for use in primary care: the Framingham Heart Study. Circulation 117, 743-753 (2008).
37. Rosenson, R. S. et al. Translation of high-density lipoprotein function into clinical practice: current prospects and future challenges. Circulation 128, 1256-1267 (2013).
38. Gotto, A. M. Jr et al. 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 (2000).
39. Nicholls, S. J. et al. Consumption of saturated fat impairs the anti-inflammatory properties of high-density lipoproteins and endothelial function. J. Am. Coll. Cardiol. 48, 715-720 (2006).
40. Sarwar, N. et al. Triglyceride-mediated pathways and coronary disease: collaborative analysis of 101 studies. Lancet 375, 1634-1639 (2010).
41. Nordestgaard, B. G. & Tybjaerg-Hansen, A. Genetic determinants of LDL, lipoprotein(a), triglyceride-rich lipoproteins and HDL: concordance and discordance with cardiovascular disease risk. Curr. Opin. Lipidol. 22, 113-122 (2011).
42. Varbo, A., Benn, M., Tybjaerg-Hansen, A. & Nordestgaard, B. G. Elevated remnant cholesterol causes both low-grade inflammation and ischemic heart disease, while elevated low-density lipoprotein cholesterol causes ischemic heart disease without inflammation. Circulation 128, 1298-1309 (2013).
43. Banka, C. L. et al. Serum amyloid A (SAA): influence on HDL-mediated cellular cholesterol efflux. J. Lipid Res. 36, 1058-1065 (1995).
44. Weichhart, T. et al. Serum amyloid A in uremic HDL promotes inflammation. J. Am. Soc. Nephrol. 23, 934-947 (2012).
45. Khovidhunkit, W. et al. Effects of infection and inflammation on lipid and lipoprotein metabolism: mechanisms and consequences to the host. J. Lipid Res. 45, 1169-1196 (2004).
46. Kontush, A. & Chapman, M. J. Functionally defective high-density lipoprotein: a new therapeutic target at the crossroads of dyslipidemia, inflammation, and atherosclerosis. Pharmacol. Rev. 58, 342-374 (2006).
47. Sharrett, A. R. et al. Coronary heart disease prediction from lipoprotein cholesterol levels, triglycerides, lipoprotein(a), apolipoproteins A-I and B, and HDL density subfractions: The Atherosclerosis Risk in Communities (ARIC) Study. Circulation 104, 1108-1113 (2001).
48. Oldoni, F., Sinke, R. J. & Kuivenhoven, J. A. Mendelian disorders of high-density lipoprotein metabolism. Circ. Res. 114, 124-142 (2014).
49. Pollin, T. I. et al. A null mutation in human APOC3 confers a favorable plasma lipid profile and apparent cardioprotection. Science 322, 1702-1705 (2008).
50. Bochem, A. E. et al. ABCA1 mutation carriers with low high-density lipoprotein cholesterol are characterized by a larger atherosclerotic burden. Eur. Heart J. 34, 286-291 (2013).
51. Anderson, J. L. & Carlquist, J. F. Genetic polymorphisms of hepatic lipase and cholesteryl ester transfer protein, intermediate phenotypes, and coronary risk: do they add up yet? J. Am. Coll. Cardiol. 41, 1990-1993 (2003).
52. van Acker, B. A. et al. 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, 161-167 (2008).
53. Johannsen, T. H. et al. Hepatic lipase, genetically elevated high-density lipoprotein, and risk of ischemic cardiovascular disease. J. Clin. Endocrinol. Metab. 94, 1264-1273 (2009).
54. Voight, B. F. et al. Plasma HDL cholesterol and risk of myocardial infarction: a Mendelian randomisation study. Lancet 380, 572-580 (2012).
55. Thompson, A. et al. Association of cholesteryl ester transfer protein genotypes with CETP mass and activity, lipid levels, and coronary risk. JAMA 299, 2777-2788 (2008).
56. Li, Y. Y. et al. Apo A5-1131T/C, FgB-455G/A,-148C/T, and CETP TaqIB gene polymorphisms and coronary artery disease in the Chinese population: a metaanalysis of 15, 055 subjects. Mol. Biol. Rep. 40, 1997-2014 (2013).
57. Dullaart, R. P. & Sluiter, W. J. Common variation in the CETP gene and the implications for cardiovascular disease and its treatment: an updated analysis. Pharmacogenomics 9, 747-763 (2008).
58. Smith, G. D. & Ebrahim, S. Mendelian randomization: prospects, potentials, and limitations. Int. J. Epidemiol. 33, 30-42 (2004).
59. Sleiman, P. M. & Grant, S. F. Mendelian randomization in the era of genomewide association studies. Clin. Chem. 56, 723-728 (2010).
60. Ward, L. D. & Kellis, M. Interpreting noncoding genetic variation in complex traits and human disease. Nature Biotech. 30, 1095-1106 (2012).
61. Holmes, M. V. et al. Mendelian randomization of blood lipids for coronary heart disease. Eur. Heart J. http://dx.doi.org/10.1093/eurheartj/eht571 (2014).
62. deGoma, E. M. & Rader, D. J. High-density lipoprotein particle number: a better measure to quantify high-density lipoprotein? J. Am. Coll. Cardiol 60, 517-520 (2012).
63. Castro, G. R. & Fielding, C. J. Early incorporation of cell-derived cholesterol into pre-beta-migrating high-density lipoprotein. Biochemistry 27, 25-29 (1988).
64. Camont, L. et al. Small, dense high-density lipoprotein-3 particles are enriched in negatively charged phospholipids: relevance to cellular cholesterol efflux, antioxidative, antithrombotic, anti-inflammatory, and antiapoptotic functionalities. Arterioscler. Thromb. Vasc. Biol. 33, 2715-2723 (2013).
65. Oram, J. F & Vaughan, A. M. ATP-binding cassette cholesterol transporters and cardiovascular disease. Circ. Res. 99, 1031-1043 (2006).
66. Rader, D. J. & Tall, A. R. The not-so-simple HDL story: Is it time to revise the HDL cholesterol hypothesis? Nature Med. 18, 1344-1346 (2012).
67. Khera, A. V. et al. Cholesterol efflux capacity, high-density lipoprotein function, and atherosclerosis. N. Engl. J. Med. 364, 127-135 (2011).
68. Hennessy, L. K., Kunitake, S. T. & Kane, J. P. Apolipoprotein A-I-containing lipoproteins, with or without apolipoprotein A-II, as progenitors of pre-beta high-density lipoprotein particles. Biochemistry 32, 5759-5765 (1993).
69. Francone, O. L, Royer, L. & Haghpassand, M. Increased prep-HDL levels, cholesterol efflux, and LCAT-mediated esterification in mice expressing the human cholesteryl ester transfer protein (CETP) and human apolipoprotein A-I (apoA-I) transgenes. J. Lipid Res. 37, 1268-1277 (1996).
70. Hattori, H. et al. Association of coronary heart disease with pre-p-HDL concentrations in Japanese men. Clin. Chem. 50, 589-595 (2004).
71. Watanabe, H. et al. Decreased high-density lipoprotein (HDL) particle size, prep-, and large HDL subspecies concentration in Finnish low-HDL families: relationship with intima-media thickness. Arterioscler. Thromb. Vasc. Biol. 26, 897-902 (2006).
72. Guey, L. T. et al. Relation of increased prep-1 high-density lipoprotein levels to risk of coronary heart disease. Am. J. Cardiol. 108, 360-366 (2011).
73. 1 HDL concentrations and low lecithin: cholesterol acyltransferase activities are strong positive risk markers for ischemic heart disease and independent of HDL-cholesterol. Clin. Chem. 56, 1128-1137 (2010).
74. Miller, N. E. et al. Lipoprotein remodeling generates lipid-poor apolipoprotein A-I particles in human interstitial fluid. Am. J. Physiol. Endocrinol. Metab. 304, E321-E328 (2013).
75. Nanjee, M. N. et al. Composition and ultrastructure of size subclasses of normal human peripheral lymph lipoproteins: quantification of cholesterol uptake by HDL in tissue fluids. J. Lipid Res. 42, 639-648 (2001).
76. Kujiraoka, T. et al. Effects of intravenous apolipoprotein A-I/phosphatidylcholine discs on LCAT, PLTP, and CETP in plasma and peripheral lymph in humans. Arterioscler. Thromb. Vasc. Biol. 23, 1653-1659 (2003).
77. Feig, J. E., Hewing, B., Smith, J. D., Hazen, S. L. & Fisher, E. A. High-density lipoprotein and atherosclerosis regression: evidence from preclinical and clinical studies. Circ. Res. 114, 205-213 (2014).
78. Diditchenko, S. et al. Novel formulation of a reconstituted high-density lipoprotein (CSL112) dramatically enhances ABCA1-dependent cholesterol efflux. Arterioscler. Thromb. Vasc. Biol. 33, 2202-2211 (2013).
79. Kontush, A. & Chapman, M. J. Antiatherogenic small, dense HDL-guardian angel of the arterial wall? Nature Clin. Pract. Cardiovasc. Med. 3, 144-153 (2006).
80. Sankaranarayanan, S. et al. Importance of macrophage cholesterol content on the flux of cholesterol mass. J. Lipid Res. 51, 3243-3249 (2010).
81. Feig, J. E. et al. HDL promotes rapid atherosclerosis regression in mice and alters inflammatory properties of plaque monocyte-derived cells. Proc. Natl Acad. Sci. USA 108, 7166-7171 (2011).
82. Cimmino, G. et al. Up-regulation of reverse cholesterol transport key players and rescue from global inflammation by ApoA-I(Milano). J. Cell. Mol. Med. 13, 3226-3235 (2009).
83. Goffinet, M. et al. Anti-atherosclerotic effect of CER-001, an engineered HDL-mimetic, in the high-fat diet-fed LDLr knock-out mouse. Circulation Abstr. 126, A18667 (2012).
84. Shaw, J. A. et al. Infusion of reconstituted high-density lipoprotein leads to acute changes in human atherosclerotic plaque. Circ. Res. 103, 1084-1091 (2008).
85. Camont, L., Chapman, M. J. & Kontush, A. Biological activities of HDL subpopulations and their relevance to cardiovascular disease. Trends Mol. Med. 17, 594-603 (2011).
86. Falk, E., Nakano, M., Bentzon, J. F., Finn, A. V. & Virmani, R. Update on acute coronary syndromes: the pathologists' view. Eur. Heart J. 34, 719-728 (2013).
87. Arbab-Zadeh, A., Nakano, M., Virmani, R. & Fuster, V. Acute coronary events. Circulation 125, 1147-1156 (2012).
88. Davies, M. J. Stability and instability: two faces of coronary atherosclerosis. The Paul Dudley White Lecture 1995. Circulation 94, 2013-2020 (1996).
89. Marso, S. P. et al. Plaque composition and clinical outcomes in acute coronary syndrome patients with metabolic syndrome or diabetes. JACC Cardiovasc. Imag. 5, S42-52 (2012).
90. Kingwell, B. A. & Chapman, M. J. The future of HDL infusion therapies: potential for clinical management of vascular disease. Circulation 128, 1112-1121 (2013).
91. Kontush, A., Lhomme, M. & Chapman, M. J. Unravelling the complexities of the HDL lipidome. J. Lipid Res. 54, 2950-2963 (2013).
92. Davidson, W. S. et al. Proteomic analysis of defined HDL subpopulations reveals particle-specific protein clusters: relevance to antioxidative function. Arterioscler. Thromb. Vasc. Biol. 29, 870-876 (2009).
93. Hattori, K. et al. Impact of statin therapy on plaque characteristics as assessed by serial OCT, grayscale and integrated backscatter-IVUS. JACC Cardiovasc. Imag. 5, 169-177 (2012).
94. Kini, A. S. et al. Changes in plaque lipid content after short-term intensive versus standard statin therapy: the YELLOW trial (reduction in yellow plaque by aggressive lipid-lowering therapy). J. Am. Coll. Cardiol. 62, 21-29 (2013).
95. Nicholls, S. J. et al. Statins, high-density lipoprotein cholesterol, and regression of coronary atherosclerosis. JAMA 297, 499-508 (2007).
96. McKenney, J. M., Proctor, J. D., Harris, S. & Chinchili, V. M. A comparison of the efficacy and toxic effects of sustained-versus immediate-release niacin in hypercholesterolemic patients. JAMA 271, 672-677 (1994).
97. Duggal, J. K. et al. Effect of niacin therapy on cardiovascular outcomes in patients with coronary artery disease. J. Cardiovasc. Pharmacol. Ther. 15, 158-166 (2010).
98. Bruckert, E., Labreuche, J. & Amarenco, P. Meta-analysis of the effect of nicotinic acid alone or in combination on cardiovascular events and atherosclerosis. Atherosclerosis 210, 353-361 (2010).
99. HPS2-THRIVE Collaborative Group. HPS2-THRIVE randomized placebo-controlled trial in 25 673 high-risk patients of ER niacin/laropiprant: trial design, pre-specified muscle and liver outcomes, and reasons for stopping study treatment.Eur. Heart J. 34, 1279-1291 (2013).
100. Boden, W. E. et al. Niacin in patients with low HDL cholesterol levels receiving intensive statin therapy. N. Engl. J. Med. 365, 2255-2267 (2011).
101. Lavigne, P. M. & Karas, R. H. The current state of niacin in cardiovascular disease prevention: a systematic review and meta-regression. J. Am. Coll. Cardiol. 61, 440-446 (2013).
102. Kobayashi, K. et al. Prostaglandin D2-DP signaling promotes endothelial barrier function via the cAMP/PKA/Tiam1/Rac1 pathway. Arterioscler. Thromb. Vasc. Biol. 33, 565-571 (2013).
103. Landmesser, U. The difficult search for a 'partner' of statins in lipid-targeted prevention of vascular events: the re-emergence and fall of niacin. Eur. Heart J. 34, 1254-1257 (2013).
104. Barter, P. J. & Rye, K. A. Is there a role for fibrates in the management of dyslipidemia in the metabolic syndrome? Arterioscler. Thromb. Vasc. Biol. 28, 39-46 (2008).
105. Veniant, M. M. et al. Defining the atherogenicity of large and small lipoproteins containing apolipoprotein B100. J. Clin. Invest. 106, 1501-1510 (2000).
106. Manninen, V. 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 85, 37-45 (1992).
107. Robins, S. J. et al. Relation of gemfibrozil treatment and lipid levels with major coronary events: VA-HIT: a randomized controlled trial. JAMA 285, 1585-1591 (2001).
108. Bezafibrate Infarction Prevention (BIP) study. Secondary prevention by raising HDL cholesterol and reducing triglycerides in patients with coronary artery disease. Circulation 102, 21-27 (2000).
109. Ginsberg, H. N. et al. Effects of combination lipid therapy in type 2 diabetes mellitus. N. Engl. J. Med. 362, 1563-1574 (2010).
110. Jun, M. et al. Effects of fibrates on cardiovascular outcomes: a systematic review and meta-analysis. Lancet 375, 1875-1884 (2010).
111. Tall, A. R. Plasma cholesteryl ester transfer protein. J. Lipid Res. 34, 1255-1274 (1993).
112. Yamashita, S. et al. Characterization of plasma lipoproteins in patients heterozygous for human plasma cholesteryl ester transfer protein (CETP) deficiency: plasma CETP regulates high-density lipoprotein concentration and composition. Metabolism 40, 756-763 (1991).
113. Inazu, A. et al. Increased high-density lipoprotein levels caused by a common cholesteryl-ester transfer protein gene mutation. N. Engl. J. Med. 323, 1234-1238 (1990).
114. Hirano, K. et al. Atherosclerotic disease in marked hyperalphalipoproteinemia. Combined reduction of cholesteryl ester transfer protein and hepatic triglyceride lipase. Arterioscler. Thromb. Vasc. Biol. 15, 1849-1856 (1995).
115. Zhong, S. 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, 2917-2923 (1996).
116. Marotti, K. R. et al. Severe atherosclerosis in transgenic mice expressing simian cholesteryl ester transfer protein. Nature 364, 73-75 (1993).
117. Fielding, C. J. & Havel, R. J. Cholesteryl ester transfer protein: friend or foe? J. Clin. Invest. 97, 2687-2688 (1996).
118. Clay, M. A., Newnham, H. H., Forte, T. M. & Barter, P. I. Cholesteryl ester transfer protein and hepatic lipase activity promote shedding of apo A-I from HDL and subsequent formation of discoidal HDL. Biochim. Biophys. Acta 1124, 52-58 (1992).
119. Foger, 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. 274, 36912-36920 (1999).
120. Hayek, T. et al. Decreased early atherosclerotic lesions in hypertriglyceridemic mice expressing cholesteryl ester transfer protein transgene. J. Clin. Invest. 96, 2071-2074 (1995).
121. Westerterp, M. et al. Cholesteryl ester transfer protein decreases high-density lipoprotein and severely aggravates atherosclerosis in APOE*3-Leiden mice. Arterioscler. Thromb. Vasc. Biol. 26, 2552-2559 (2006).
122. Okamoto, H. et al. A cholesteryl ester transfer protein inhibitor attenuates atherosclerosis in rabbits. Nature 406, 203-207 (2000).
123. Huang, Z., Inazu, A., Nohara, A., Higashikata, T. & Mabuchi, H. Cholesteryl ester transfer protein inhibitor (JTT-705) and the development of atherosclerosis in rabbits with severe hypercholesterolaemia. Clin. Sci. 103, 587-594 (2002).
124. Regieli, J. J. et al. CETP genotype predicts increased mortality in statin-treated men with proven cardiovascular disease: an adverse pharmacogenetic interaction. Eur. Heart J. 29, 2792-2799 (2008).
125. Ordovas, J. M. et al. Association of cholesteryl ester transfer protein-TaqIB polymorphism with variations in lipoprotein subclasses and coronary heart disease risk: the Framingham study. Arterioscler. Thromb. Vasc. Biol. 20, 1323-1329 (2000).
126. Barter, P. J. et al. Effects of torcetrapib in patients at high risk for coronary events. N. Engl. J. Med. 357, 2109-2122 (2007).
127. Schwartz, G. G. et al. Effects of dalcetrapib in patients with a recent acute coronary syndrome. N. Engl. J. Med. 367, 2089-2099 (2012).
128. Ballantyne, C. M. et al. Effect of dalcetrapib plus pravastatin on lipoprotein metabolism and high-density lipoprotein composition and function in dyslipidemic patients: results of a phase IIb dose-ranging study. Am. Heart J. 163, 515-521.e3 (2012).
129. Villard, E. F. et al. Elevated CETP activity improves plasma cholesterol efflux capacity from human macrophages in women. Arterioscler. Thromb. Vasc. Biol. 32, 2341-2349 (2012).
130. Yamashita, S. et al. Very high density lipoproteins induced by plasma cholesteryl ester transfer protein (CETP) have a potent antiatherogenic function. Ann. NY Acad. Sci. 748, 606-608 (1995).
131. Kathiresan, S. Will cholesteryl ester transfer protein inhibition succeed primarily by lowering low-density lipoprotein cholesterol? Insights from human genetics and clinical trials. J. Am. Coll. Cardiol. 60, 2049-2052 (2012).
132. Borggreve, S. E. et al. The ability of plasma to stimulate fibroblast cholesterol efflux is associated with the-629C→A cholesteryl ester transfer protein promoter polymorphism: role of lecithin: cholesterol acyltransferase activity. Biochim. Biophys. Acta 1781, 10-15 (2008).
133. Siebel, A. L. et al. Effects of high-density lipoprotein elevation with cholesteryl ester transfer protein inhibition on insulin secretion. Circ. Res. 113, 167-175 (2013).
134. Atger, V. et al. Cholesterol efflux potential of sera from mice expressing human cholesteryl ester transfer protein and/or human apolipoprotein AI. J. Clin. Invest. 96, 2613-2622 (1995).
135. Matsuura, F., Wang, N., Chen, W., Jiang, X. C. & Tall, A. R. HDL from CETP-deficient subjects shows enhanced ability to promote cholesterol efflux from macrophages in an apoE-and ABCG1-dependent pathway. J. Clin. Invest. 116, 1435-1442 (2006).
136. Ishigami, M. et al. Large and cholesteryl ester-rich high-density lipoproteins in cholesteryl ester transfer protein (CETP) deficiency can not protect macrophages from cholesterol accumulation induced by acetylated low-density lipoproteins. J. Biochem. 116, 257-262 (1994).
137. Tanigawa, H. et al. Expression of cholesteryl ester transfer protein in mice promotes macrophage reverse cholesterol transport. Circulation 116, 1267-1273 (2007).
138. Tchoua, U. et al. The effect of cholesteryl ester transfer protein overexpression and inhibition on reverse cholesterol transport. Cardiovasc. Res. 77, 732-739 (2008).
139. Brousseau, M. E. 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, 1057-1064 (2005).
140. Marschang, P. et al. Plasma cholesteryl ester transfer protein concentrations predict cardiovascular events in patients with coronary artery disease treated with pravastatin. J. Intern. Med. 260, 151-159 (2006).
141. Vasan, R. S. et al. Association of circulating cholesteryl ester transfer protein activity with incidence of cardiovascular disease in the community. Circulation 120, 2414-2420 (2009).
142. Khera, A. V., Wolfe, M. L., Cannon, C. P., Qin, J. & Rader, D. J. On-statin cholesteryl ester transfer protein mass and risk of recurrent coronary events (from the pravastatin or atorvastatin evaluation and infection therapy-thrombolysis in myocardial infarction 22 [PROVE IT-TIMI 22] study. Am. J. Cardiol. 106, 451-456 (2010).
143. Duwensee, K. et al. Cholesteryl ester transfer protein in patients with coronary heart disease. Eur. J. Clin. Invest. 40, 616-622 (2010).
144. Ritsch, A. et al. Cholesteryl ester transfer protein and mortality in patients undergoing coronary angiography: the Ludwigshafen Risk and Cardiovascular Health study. Circulation 121, 366-374 (2010).
145. Robins, S. J., Lyass, A., Brocia, R. W., Massaro, J. M. & Vasan, R. S. Plasma lipid transfer proteins and cardiovascular disease. The Framingham Heart Study. Atherosclerosis 228, 230-236 (2013).
146. Boekholdt, S. M. et al. Plasma levels of cholesteryl ester transfer protein and the risk of future coronary artery disease in apparently healthy men and women: the prospective EPIC (European Prospective Investigation into Cancer and nutrition)-Norfolk population study. Circulation 110, 1418-1423 (2004).
147. Borggreve, S. E. et al. High plasma cholesteryl ester transfer protein levels may favour reduced incidence of cardiovascular events in men with low triglycerides. Eur. Heart J. 28, 1012-1018 (2007).
148. Kappelle, P. J., Perton, F., Hillege, H. L., Dallinga-Thie, G. M. & Dullaart, R. P. High plasma cholesteryl ester transfer but not CETP mass predicts incident cardiovascular disease: a nested case-control study. Atherosclerosis 217, 249-252 (2011).
149. Schierer, A. et al. Genetic variation in cholesterol ester transfer protein, serum CETP activity, and coronary artery disease risk in Asian Indian diabetic cohort. Pharmacogenet. Genom. 22, 95-104 (2012).
150. Liang, H. Q., Rye, K. A. & Barter, P. J. Dissociation of lipid-free apolipoprotein A-I from high density lipoproteins. J. Lipid Res. 35, 1187-1199 (1994).
151. Cazita, P. M., Barbeiro, D. F., Moretti, A. I., Quintao, E. C. & Soriano, F. G. Human cholesteryl ester transfer protein expression enhances the mouse survival rate in an experimental systemic inflammation model: a novel role for CETP. Shock 30, 590-595 (2008).
152. Bishop, B. M. Systematic review of CETP inhibitors for increasing high-density lipoprotein cholesterol: where do these agents stand in the approval process? Am. J. Ther. (in the press).
153. Bloomfield, D. et al. Efficacy and safety of the cholesteryl ester transfer protein inhibitor anacetrapib as monotherapy and coadministered with atorvastatin in dyslipidemic patients. Am. Heart J. 157, 352-360.e2 (2009).
154. Krauss, R. M. et al. Changes in lipoprotein subfraction concentration and composition in healthy individuals treated with the CETP inhibitor anacetrapib. J. Lipid Res. 53, 540-547 (2012).
155. Nicholls, S. J. et al. Effects of the CETP inhibitor evacetrapib administered as monotherapy or in combination with statins on HDL and LDL cholesterol: a randomized controlled trial. JAMA 306, 2099-2109 (2011).
156. Cannon, C. P. et al. Safety of anacetrapib in patients with or at high risk for coronary heart disease. N. Engl. J. Med. 363, 2406-2415 (2010).
157. Yvan-Charvet, L. et al. Cholesterol efflux potential and antiinflammatory properties of high-density lipoprotein after treatment with niacin or anacetrapib. Arterioscler. Thromb. Vasc. Biol. 30, 1430-1438 (2010).
158. Heinecke, J. W. The not-so-simple HDL story: a new era for quantifying HDL and cardiovascular risk? Nature Med. 18, 1346-1347 (2012).
159. Larach, D. B., deGoma, E. M. & Rader, D. J. Targeting high density lipoproteins in the prevention of cardiovascular disease? Curr. Cardiol. Rep. 14, 684-691 (2012).
160. Vucic, E. & Rosenson, R. S. Recombinant high-density lipoprotein formulations. Curr. Atheroscler. Rep. 13, 81-87 (2011).
161. Nanjee, M. N., Doran, J. E., Lerch, P. G. & Miller, N. E. Acute effects of intravenous infusion of ApoA1/phosphatidylcholine discs on plasma lipoproteins in humans. Arterioscler. Thromb. Vasc. Biol. 19, 979-989 (1999).
162. Gille, A., Easton, R., Wright, S. & Shear, C. CSL112, a novel formulation of human apolipoprotein A-I, dramatically increases cholesterol efflux capacity in healthy subjects: a placebo-controlled, double-blinded, randomized single ascending dose study. Circulation Abstr. 126, A11855 (2012).
163. Keyserling, C. H. et al. CER-001, a synthetic HDL-mimetic, safely mobilizes cholesterol in healthy dyslipidemic volunteers. Circulation Abstr. 124, A15525 (2011).
164. Nanjee, M. N. et al. Intravenous apoA-I/lecithin discs increase pre-β-HDL concentration in tissue fluid and stimulate reverse cholesterol transport in humans. J. Lipid Res. 42, 1586-1593 (2001).
165. Kee, P., Rye, K. A., Taylor, J. L., Barrett, P. H. & Barter, P. J. Metabolism of apoA-I as lipid-free protein or as component of discoidal and spherical reconstituted HDLs: studies in wild-type and hepatic lipase transgenic rabbits. Arterioscler. Thromb. Vasc. Biol. 22, 1912-1917 (2002).
166. Easton, R., Tremper, L. & Shear, C. Safety and pharmakokinetics of a novel formulation of human apolipoprotein A-I (CSL112) in healthy subjects: results of a placebo-controlled, randomized multiple ascending dose study. Circulation 126, A11892 (2012).
167. Nicholls, S. J. et al. Relationship between atheroma regression and change in lumen size after infusion of apolipoprotein A-I Milano. J. Am. Coll. Cardiol. 47, 992-997 (2006).
168. Nissen, S. E. 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).
169. Tardif, J. C. et al. Effects of reconstituted high-density lipoprotein infusions on coronary atherosclerosis: a randomized controlled trial. JAMA 297, 1675-1682 (2007).
170. Waksman, R. et al. A first-in-man, randomized, placebo-controlled study
171. Drew, B. G. et al. Reconstituted high-density lipoprotein infusion modulates fatty acid metabolism in patients with type 2 diabetes mellitus. J. Lipid Res. 52, 572-581 (2011).
172. Hoang, A. et al. Mechanism of cholesterol efflux in humans after infusion of reconstituted high-density lipoprotein. Eur. Heart J. 33, 657-665 (2012).
173. Tricoci, P. et al. Safety and tolerability of CSL112 in subjects with stable atherothrombotic disease: esults from a phase 2a multicenter, randomized, double-blind, placebo-controlled, ascending dose study. Circulation Abstr. A18589 (2013).
174. Gille, A. et al. A novel formualtion of human apolipoprotein A-I dramatically increases cholesterol efflux capacity in patients with stable atherothrombotic disease: a multicenter, randomized, double-blind, placebo-controlled, ascending-dose study. Circulation Abstr. A15780 (2013).
175. Kunnen, S. & Van Eck, M. Lecithin:cholesterol acyltransferase: old friend or foe in atherosclerosis? J. Lipid Res. 53, 1783-1799 (2012).
176. Rousset, X. et al. Effect of recombinant human lecithin cholesterol acyltransferase infusion on lipoprotein metabolism in mice. J. Pharmacol. Exp. Ther. 335, 140-148 (2010).
177. Mertens, A. et al. Increased low-density lipoprotein oxidation and impaired high-density lipoprotein antioxidant defense are associated with increased macrophage homing and atherosclerosis in dyslipidemic obese mice: LCAT gene transfer decreases atherosclerosis. Circulation 107, 1640-1646 (2003).
178. Furbee, J. W. Jr., Sawyer, J. K. & Parks, J. S. Lecithin:cholesterol acyltransferase deficiency increases atherosclerosis in the low density lipoprotein receptor and apolipoprotein E knockout mice. J. Biol. Chem. 277, 3511-3519 (2002).
179. Berard, A. M. et al. High plasma HDL concentrations associated with enhanced atherosclerosis in transgenic mice overexpressing lecithin-cholesteryl acyltransferase. Nature Med. 3, 744-749 (1997).
180. Furbee, J. W. Jr & Parks, J. S. Transgenic overexpression of human lecithin: cholesterol acyltransferase (LCAT) in mice does not increase aortic cholesterol deposition. Atherosclerosis 165, 89-100 (2002).
181. Mehlum, A., Muri, M., Hagve, T. A., Solberg, L. A. & Prydz, H. Mice overexpressing human lecithin: cholesterol acyltransferase are not protected against diet-induced atherosclerosis. APMIS 105, 861-868 (1997).
182. Holleboom, A. G. et al. Plasma levels of lecithin:cholesterol acyltransferase and risk of future coronary artery disease in apparently healthy men and women: a prospective case-control analysis nested in the EPIC-Norfolk population study. J. Lipid Res. 51, 416-421 (2010).
183. Bailey, D. et al. RVX-208: a small molecule that increases apolipoprotein A-I and high-density lipoprotein cholesterol in vitro and in vivo. J. Am. Coll. Cardiol. 55, 2580-2589 (2010).
184. Nicholls, S. J. et al. Efficacy and safety of a novel oral inducer of apolipoprotein A-I synthesis in statin-treated patients with stable coronary artery disease a randomized controlled trial. J. Am. Coll. Cardiol. 57, 1111-1119 (2011).
185. Nicholls, S. J. et al. ApoA-I induction as a potential cardioprotective strategy: rationale for the SUSTAIN and ASSURE studies. Cardiovasc. Drugs Ther. 26, 181-187 (2012).
186. Nicholls, S. J. et al. ASSURE: effect of an oral agent indusing apoA-I synthesis on progression of coronary atheroslerosis: results of the ASSURE study. [online] http://congress365.escardio.org/Search-Results?vgnextkeyword= ASSURE (2013).
187. Navab, M. et al. Apolipoprotein A-I mimetic peptides. Arterioscler. Thromb. Vasc. Biol. 25, 1325-1331 (2005).
188. Carballo-Jane, E. et al. ApoA-I mimetic peptides promote pre-β HDL formation in vivo causing remodeling of HDL and triglyceride accumulation at higher dose. Bioorg. Med. Chem. 18, 8669-8678 (2010).
189. Chen, X. et al. An apoA-I mimetic peptide increases LCAT activity in mice through increasing HDL concentration. Int. J. Biol. Sci. 5, 489-499 (2009).
190. Song, X., Fischer, P., Chen, X., Burton, C. & Wang, J. An apoA-I mimetic peptide facilitates off-loading cholesterol from HDL to liver cells through scavenger receptor BI. Int. J. Biol. Sci. 5, 637-646 (2009).
191. Navab, M., Anantharamaiah, G. M. & Fogelman, A. M. The effect of apolipoprotein mimetic peptides in inflammatory disorders other than atherosclerosis. Trends Cardiovasc. Med. 18, 61-66 (2008).
192. Remaley, A. T., Amar, M. & Sviridov, D. HDL-replacement therapy: mechanism of action, types of agents and potential clinical indications. Expert Rev. Cardiovasc. Ther. 6, 1203-1215 (2008).
193. Verschuren, L., de Vries-van der Weij, J., Zadelaar, S., Kleemann, R. & Kooistra, T. LXR agonist suppresses atherosclerotic lesion growth and promotes lesion regression in apoE*3Leiden mice: time course and mechanisms. J. Lipid Res. 50, 301-311 (2009).
194. Beltowski, J. Liver X receptors (LXR) as therapeutic targets in dyslipidemia. Cardiovasc. Ther. 26, 297-316 (2008).
195. Ogata, M. et al. On the mechanism for PPAR agonists to enhance ABCA1 gene expression. Atherosclerosis 205, 413-419 (2009).
196. Hafiane, A. & Genest, J. HDL atherosclerosis, and emerging therapies. Cholesterol 2013, 891403 (2013).
197. Mencarelli, A. & Fiorucci, S. FXR an emerging therapeutic target for the treatment of atherosclerosis. J. Cell. Mol. Med. 14, 79-92 (2010).
198. -/-) mice. J. Pharmacol. Exp. Ther. 343, 556-567 (2012).
199. Goodman, K. B. et al. Discovery of potent, selective sulfonylfuran urea endothelial lipase inhibitors. Bioorg. Med. Chem. Lett. 19, 27-30 (2009).
200. O'Connell, D. P. et al. Design and synthesis of boronic acid inhibitors of endothelial lipase. Bioorg. Med. Chem. Lett. 22, 1397-1401 (2012).
201. Rayner, K. J. & Moore, K. J. MicroRNA control of high-density lipoprotein metabolism and function. Circ. Res. 114, 183-192 (2014).
202. Rayner, K. J. et al. MiR-33 contributes to the regulation of cholesterol homeostasis. Science 328, 1570-1573 (2010).
203. Rayner, K. J. et al. Antagonism of miR-33 in mice promotes reverse cholesterol transport and regression of atherosclerosis. J. Clin. Invest. 121, 2921-2931 (2011).
204. -/- mice. J. Am. Heart Assoc. 1, e003376 (2012).
205. -/- mice. J. Lipid Res. 54, 2647-2657 (2013).
206. Graham, M. J. et al. Antisense oligonucleotide inhibition of apolipoprotein C-III reduces plasma triglycerides in rodents, nonhuman primates, and humans. Circ. Res. 112, 1479-1490 (2013).
207. Fu, Y. et al. ABCA12 regulates ABCA1-dependent cholesterol efflux from macrophages and the development of atherosclerosis. Cell. Metab. 18, 225-238 (2013).
208. Rayner, K. J. et al. Inhibition of miR-33a/b in non-human primates raises plasma HDL and lowers VLDL triglycerides. Nature 478, 404-407 (2011).
209. Vickers, K. C., Palmisano, B. T., Shoucri, B. M., Shamburek, R. D. & Remaley, A. T. MicroRNAs are transported in plasma and delivered to recipient cells by high-density lipoproteins. Nature Cell Biol. 13, 423-433 (2011).
210. Chapman, M. J., Assmann, G., Fruchart, J. C., Shepherd, J. & Sirtori, C. Raising high-density lipoprotein cholesterol with reduction of cardiovascular risk: the role of nicotinic acid-a position paper developed by the European Consensus Panel on HDL-C. Curr. Med. Res. Opin. 20, 1253-1268 (2004).
211. National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). Third report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III)-final report. Circulation 106, 3143-3421 (2002).
212. Contois, J. et al. Reference intervals for plasma apolipoprotein A-1 determined with a standardized commercial immunoturbidimetric assay: results from the Framingham Offspring Study. Clin. Chem. 42, 507-514 (1996).
213. Silva, R. A. et al. Structure of apolipoprotein A-I in spherical high density lipoproteins of different sizes. Proc. Natl Acad. Sci. USA 105, 12176-12181 (2008).
214. Rosenson, R. S. et al. HDL measures, particle heterogeneity, proposed nomenclature, and relation to atherosclerotic cardiovascular events. Clin. Chem. 57, 392-410 (2011).
215. Martinez, L. O. et al. Ectopic β-chain of ATP synthase is an apolipoprotein A-I receptor in hepatic HDL endocytosis. Nature 421, 75-79 (2003).
216. Fielding, C. J. & Fielding, P. E. Molecular physiology of reverse cholesterol transport. J. Lipid Res. 36, 211-228 (1995).
217. Lewis, G. F. & Rader, D. J. New insights into the regulation of HDL metabolism and reverse cholesterol transport. Circ. Res. 96, 1221-1232 (2005).
218. Smith, J. D. Insight into ABCG1-mediated cholesterol efflux. Arterioscler. Thromb. Vasc. Biol. 26, 1198-1200 (2006).
219. Rye, K. A., Bursill, C. A., Lambert, G., Tabet, F. & Barter, P. J. The metabolism and anti-atherogenic properties of HDL. J. Lipid Res. 50, S195-S200 (2009).
220. Lamon-Fava, S. et al. Extended-release niacin alters the metabolism of plasma apolipoprotein (Apo) A-I and ApoB-containing lipoproteins. Arterioscler. Thromb. Vasc. Biol. 28, 1672-1678 (2008).
221. Chapman, M. J. et al. Triglyceride-rich lipoproteins and high-density lipoprotein cholesterol in patients at high risk of cardiovascular disease: evidence and guidance for management. Eur. Heart J. 32, 1345-1361 (2011).
222. Wagner, J. et al. Characterization of levels and cellular transfer of circulating lipoprotein-bound microRNAs. Arterioscler. Thromb. Vasc. Biol. 33, 1392-1400 (2013).
223. Chen, W. J. et al. MicroRNA-33 in atherosclerosis etiology and pathophysiology. Atherosclerosis 227, 201-208 (2013).
224. Najafi-Shoushtari, S. H. et al. MicroRNA-33 and the SREBP host genes cooperate to control cholesterol homeostasis. Science 328, 1566-1569 (2010).
225. Barter, P. J., Brandrup-Wognsen, G., Palmer, M. K. & Nicholls, S. J. Effect of statins on HDL-C: a complex process unrelated to changes in LDL-C: analysis of the VOYAGER Database. J. Lipid Res. 51, 1546-1553 (2010).