High-density lipoprotein: Vascular protective effects, dysfunction, and potential as therapeutic target

Circulation Research

Volumn 114, Issue 1, 2014, Pages 171-182

  Lüscher, Thomas F ^a,c   Landmesser, Ulf ^a,c   Von Eckardstein, Arnold ^b   Fogelman, Alan M ^d,e  

^a UNIVERSITY HOSPITAL ZURICH   (Switzerland)

^b UNIVERSITY HOSPITAL ZURICH   (Switzerland)

^c UNIVERSITY OF ZURICH   (Switzerland)

^d UNIVERSITY OF CALIFORNIA   (United States)

^e UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

apolipoprotein A I; cholesterol; HDL; nitric oxide

Indexed keywords

AMINO ACID; ANACETRAPIB; CHOLESTEROL; CHOLESTEROL ESTER TRANSFER PROTEIN; CHOLESTEROL ESTER TRANSFER PROTEIN INHIBITOR; DALCETRAPIB; EVACETRAPIB; EZETIMIBE; HIGH DENSITY LIPOPROTEIN; HIGH DENSITY LIPOPROTEIN CHOLESTEROL; LAROPIPRANT; LIPOPROTEIN; NICOTINIC ACID; PEPTIDE; PIOGLITAZONE; PLACEBO; ROSIGLITAZONE; SIMVASTATIN; TORCETRAPIB;

ACUTE CORONARY SYNDROME; CHOLESTEROL TRANSPORT; CORONARY ARTERY DISEASE; ENDOTHELIUM CELL; EPIDEMIOLOGICAL DATA; HEART PROTECTION; HUMAN; HYPERCHOLESTEROLEMIA; IN VITRO STUDY; LIPOPROTEIN METABOLISM; MACROPHAGE; NONHUMAN; OUTCOME ASSESSMENT; PRIORITY JOURNAL; REVIEW; VASCULAR DISEASE;

EID: 84892907535     PISSN: 00097330     EISSN: 15244571     Source Type: Journal    
DOI: 10.1161/CIRCRESAHA.114.300935     Document Type: Review

References (114)

1. Sharrett AR, Ballantyne CM, Coady SA, Heiss G, Sorlie PD, Catellier D, Patsch W. 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. 2001;104:1108-1113.
2. Gordon T, Castelli WP, Hjortland MC, Kannel WB, Dawber TR. High density lipoprotein as a protective factor against coronary heart disease. The Framingham Study. Am J Med. 1977;62:707-714.
3. Gordon DJ, Probstfeld JL, Garrison RJ, Neaton JD, Castelli WP, Knoke JD, Jacobs DR Jr, Bangdiwala S, Tyroler HA. High-density lipoprotein cholesterol and cardiovascular disease. Four prospective American studies. Circulation. 1989;79:8-15.
4. Di Angelantonio E, Sarwar N, Perry P, Kaptoge S, Ray KK, Thompson A, Wood AM, Lewington S, Sattar N, Packard CJ, Collins R, Thompson SG, Danesh J. Major lipids, apolipoproteins, and risk of vascular disease. JAMA. 2009;302:1993-2000.
5. Barter P, Gotto AM, LaRosa JC, Maroni J, Szarek M, Grundy SM, Kastelein JJ, Bittner V, Fruchart JC; Treating to New Targets Investigators. HDL cholesterol, very low levels of LDL cholesterol, and cardiovascular events. N Engl J Med. 2007;357:1301-1310.
6. Linsel-Nitschke P, Tall AR. HDL as a target in the treatment of atheroscle-roti c cardiovascular disease. Nat Rev Drug Discov. 2005;4:193-205.
7. Ginsberg HN, Elam MB, Lovato LC, et al. Effects of combination lipid therapy in type 2 diabetes mellitus. N Engl J Med. 2010;362:1563-1574.
8. Barter PJ, Caulfeld M, Eriksson M, et al; ILLUMINATE Investigators. Effects of torcetrapib in patients at high risk for coronary events. N Engl J Med. 2007;357:2109-2122.
9. Boden WE, Probstfeld JL, Anderson T, Chaitman BR, Desvignes-Nickens P, Koprowicz K, McBride R, Teo K, Weintraub W; AIM-HIGH Investigators. Niacin in patients with low HDL cholesterol levels receiving intensive statin therapy. N Engl J Med. 2011;365:2255-2267.
10. Schwartz GG, Olsson AG, Abt M, et al; dal-OUTCOMES Investigators. Effects of dalcetrapib in patients with a recent acute coronary syndrome. N Engl J Med. 2012;367:2089-2099.
11. von Eckardstein A. Implications of torcetrapib failure for the future of HDL therapy: is HDL-cholesterol the right target? Expert Rev Cardiovasc Ther. 2010;8:345-358.
12. Besler C, Lüscher TF, Landmesser U. Molecular mechanisms of vascular effects of High-density lipoprotein: alterations in cardiovascular disease. EMBO Mol Med. 2012;4:251-268.
13. Voight BF, Peloso GM, Orho-Melander M, et al. Plasma HDL cholesterol and risk of myocardial infarction: a mendelian randomisation study. Lancet. 2012;380:572-580.
14. Varbo A, Benn M, Tybjærg-Hansen A, Jørgensen AB, Frikke-Schmidt R, Nordestgaard BG. Remnant cholesterol as a causal risk factor for ischemic heart disease. J Am Coll Cardiol. 2013;61:427-436.
15. Huang R, Silva RA, Jerome WG, Kontush A, Chapman MJ, Curtiss LK, Hodges TJ, Davidson WS. Apolipoprotein A-I structural organization in high-density li-poproteins isolated from human plasma. Nat Struct Mol Biol. 2011;18:416-422.
16. Rosenson RS, Brewer HB Jr, Chapman MJ, Fazio S, Hussain MM, Kontush A, Krauss RM, Otvos JD, Remaley AT, Schaefer EJ. HDL measures, particle heterogeneity, proposed nomenclature, and relation to atherosclerotic cardiovascular events. Clin Chem. 2011;57:392-410.
17. Rye KA, Barter PJ. Predictive value of different HDL particles for the protection against or risk of coronary heart disease. Biochim Biophys Acta. 2012;1821:473-480.
18. Mackey RH, Greenland P, Goff DC Jr, Lloyd-Jones D, Sibley CT, Mora S. High-density lipoprotein cholesterol and particle concentrations, carotid atherosclerosis, and coronary events: MESA (multi-ethnic study of atherosclerosis). J Am Coll Cardiol. 2012;60:508-516.
19. Vaisar T, Pennathur S, Green PS, et al. Shotgun proteomics implicates protease inhibition and complement activation in the antiinfammatory properties of HDL. J Clin Invest. 2007;117:746-756.
20. Davidson WS, Silva RA, Chantepie S, Lagor WR, Chapman MJ, Kontush A. Proteomic analysis of defned HDL subpopulations reveals particle-specifc protein clusters: relevance to antioxidative function. Arterioscler Thromb Vasc Biol. 2009;29:870-876.
21. Shah AS, Tan L, Lu Long J, Davidson WS. The proteomic diversity of high density lipoproteins: Our emerging understanding of its importance in lipid transport and beyond. J Lipid Res. 2013;54:2575-2585.
22. Wiesner P, Leidl K, Boettcher A, Schmitz G, Liebisch G. Lipid profling of FPLC-separated lipoprotein fractions by electrospray ionization tandem mass spectrometry. J Lipid Res. 2009;50:574-585.
23. Vickers KC, Palmisano BT, Shoucri BM, Shamburek RD, Remaley AT. MicroRNAs are transported in plasma and delivered to recipient cells by high-density lipoproteins. Nat Cell Biol. 2011;13:423-433.
24. Wagner J, Riwanto M, Besler C, Knau A, Fichtlscherer S, Röxe T, Zeiher AM, Landmesser U, Dimmeler S. Characterization of levels and cellular transfer of circulating lipoprotein-bound microRNAs. Arterioscler Thromb Vasc Biol. 2013;33:1392-1400.
25. Ansell BJ, Navab M, Hama S, Kamranpour N, Fonarow G, Hough G, Rahmani S, Mottahedeh R, Dave R, Reddy ST, Fogelman AM. Infammatory/antiinfammatory properties of high-density lipoprotein distinguish patients from control subjects better than high-density lipopro-tein cholesterol levels and are favorably affected by simvastatin treatment. Circulation. 2003;108:2751-2756.
26. Sorrentino SA, Besler C, Rohrer L, et al. Endothelial-vasoprotective effects of high-density lipoprotein are impaired in patients with type 2 diabetes mellitus but are improved after extended-release niacin therapy. Circulation. 2010;121:110-122.
27. Besler C, Heinrich K, Rohrer L, et al. Mechanisms underlying adverse effects of HDL on eNOS-activating pathways in patients with coronary artery disease. J Clin Invest. 2011;121:2693-2708.
28. Riwanto M, Rohrer L, Roschitzki B, Besler C, Mocharla P, Mueller M, Perisa D, Heinrich K, Altwegg L, von Eckardstein A, Lüscher TF, Landmesser U. Altered activation of endothelial anti-and proapop-totic pathways by high-density lipoprotein from patients with coronary artery disease: role of high-density lipoprotein-proteome remodeling. Circulation. 2013;127:891-904.
29. Speer T, Rohrer L, Blyszczuk P, et al. Abnormal high-density lipoprotein induces endothelial dysfunction via activation of Toll-like receptor-2. Immunity. 2013;38:754-768.
30. Fisher EA, Feig JE, Hewing B, Hazen SL, Smith JD. High-density lipopro-tein function, dysfunction, and reverse cholesterol transport. Arterioscler Thromb Vasc Biol. 2012;32:2813-2820.
31. Marsche G, Saemann MD, Heinemann A, Holzer M. Infammation alters HDL composition and function: implications for HDL-raising therapies. Pharmacol Ther. 2013;137:341-351.
32. Khera AV, Cuchel M, de la Llera-Moya M, Rodrigues A, Burke MF, Jafri K, French BC, Phillips JA, Mucksavage ML, Wilensky RL, Mohler ER, Rothblat GH, Rader DJ. Cholesterol effux capacity, high-density lipopro-tein function, and atherosclerosis. N Engl J Med. 2011;364:127-135.
33. Rosenson RS, Brewer HB Jr, Davidson WS, Fayad ZA, Fuster V, Goldstein J, Hellerstein M, Jiang XC, Phillips MC, Rader DJ, Remaley AT, Rothblat GH, Tall AR, Yvan-Charvet L. Cholesterol effux and atheroprotection: advancing the concept of reverse cholesterol transport. Circulation. 2012;125:1905-1919.
34. Martinez LO, Jacquet S, Esteve JP, Rolland C, Cabezón E, Champagne E, Pineau T, Georgeaud V, Walker JE, Tercé F, Collet X, Perret B, Barbaras R. Ectopic beta-chain of ATP synthase is an apolipoprotein A-I receptor in hepatic HDL endocytosis. Nature. 2003;421:75-79.
35. Serhan N, Cabou C, Verdier C, Lichtenstein L, Malet N, Perret B, Laffargue M, Martinez LO. Chronic pharmacological activation of P2Y13 receptor in mice decreases HDL-cholesterol level by increasing hepatic HDL uptake and bile acid secretion. Biochim Biophys Acta. 2013;1831:719-725.
36. Cavelier C, Ohnsorg PM, Rohrer L, von Eckardstein A. The β-chain of cell surface F(0)F(1) ATPase modulates apoA-I and HDL transcytosis through aortic endothelial cells. Arterioscler Thromb Vasc Biol. 2012;32:131-139.
37. Graversen JH, Castro G, Kandoussi A, Nielsen H, Christensen EI, Norden A, Moestrup SK. A pivotal role of the human kidney in catabolism of HDL protein components apolipoprotein A-I and A-IV but not of A-II. Lipids. 2008;43:467-470.
38. Glomset JA, Wright JL. Some properties of a cholesterol esterifying enzyme in human plasma. Biochim Biophys Acta. 1964;89:266-276.
39. Jakobsson T, Treuter E, Gustafsson JÅ, Steffensen KR. Liver X receptor biology and pharmacology: new pathways, challenges and opportunities. Trends Pharmacol Sci. 2012;33:394-404.
40. Tarling EJ, Edwards PA. ATP binding cassette transporter G1 (ABCG1) is an intracellular sterol transporter. Proc Natl Acad Sci USA. 2011; 108:19719-19724.
41. Ramirez CM, Rotllan N, Vlassov AV, Davalos A, Li M, Goedeke L, Aranda JF, Cirera-Salinas D, Araldi E, Salerno A, Wanschel AC, Zavadil J, Castrillo A, Jungsu K, Suarez Y, Fernandez-Hernando C. Control of cholesterol metabolism and plasma HDL levels by miRNA-144. Circ Res. 2013.
42. Moore KJ. microRNAs: small regulators with a big impact on lipid metabolism. J Lipid Res. 2013;54:1159-1160.
43. Tall AR, Yvan-Charvet L, Westerterp M, Murphy AJ. Cholesterol effux: a novel regulator of myelopoiesis and atherogenesis. Arterioscler Thromb Vasc Biol. 2012;32:2547-2552.
44. Murphy AJ, Bijl N, Yvan-Charvet L, Welch CB, Bhagwat N, Reheman A, Wang Y, Shaw JA, Levine RL, Ni H, Tall AR, Wang N. Cholesterol effux in megakaryocyte progenitors suppresses platelet production and throm-bocytosis. Nat Med. 2013;19:586-594.
45. Westerterp M, Murphy AJ, Wang M, et al. Defciency of abca1 and abcg1 in macrophages increases infammation and accelerates atherosclerosis in mice. Circ Res. 2013;112:1456-1465.
46. Sorci-Thomas MG, Thomas MJ. High density lipoprotein biogenesis, cholesterol effux, and immune cell function. Arterioscler Thromb Vasc Biol. 2012;32:2561-2565.
47. Terasaka N, Westerterp M, Koetsveld J, Fernández-Hernando C, Yvan-Charvet L, Wang N, Sessa WC, Tall AR. ATP-binding cassette transporter G1 and high-density lipoprotein promote endothelial NO synthesis through a decrease in the interaction of caveolin-1 and endothelial NO synthase. Arterioscler Thromb Vasc Biol. 2010;30:2219-2225.
48. Kruit JK, Wijesekara N, Westwell-Roper C, Vanmierlo T, de Haan W, Bhattacharjee A, Tang R, Wellington CL, LütJohann D, Johnson JD, Brunham LR, Verchere CB, Hayden MR. Loss of both ABCA1 and ABCG1 results in increased disturbances in islet sterol homeostasis, in-fammation, and impaired β-cell function. Diabetes. 2012;61:659-664.
49. Clee SM, Kastelein JJ, van Dam M, et al. Age and residual cholesterol ef-fux affect HDL cholesterol levels and coronary artery disease in ABCA1 heterozygotes. J Clin Invest. 2000;106:1263-1270.
50. von Eckardstein A, Huang Y, Wu S, Funke H, Noseda G, Assmann G. Reverse cholesterol transport in plasma of patients with different forms of familial HDL defciency. Arterioscler Thromb Vasc Biol. 1995;15:691-703.
51. Eckardstein A. Tachometer for reverse cholesterol transport? J Am Heart Assoc. 2012;1:e003723.
52. Dietschy JM, Turley SD. Control of cholesterol turnover in the mouse. J Biol Chem. 2002;277:3801-3804.
53. Haghpassand M, Bourassa PA, Francone OL, Aiello RJ. Monocyte/mac-rophage expression of ABCA1 has minimal contribution to plasma HDL levels. J Clin Invest. 2001;108:1315-1320.
54. Brunham LR, Singaraja RR, Duong M, Timmins JM, Fievet C, Bissada N, Kang MH, Samra A, Fruchart JC, McManus B, Staels B, Parks JS, Hayden MR. Tissue-specifc roles of ABCA1 infuence susceptibility to atherosclerosis. Arterioscler Thromb Vasc Biol. 2009;29:548-554.
55. Zhang Y, Zanotti I, Reilly MP, Glick JM, Rothblat GH, Rader DJ. Overexpression of apolipoprotein A-I promotes reverse transport of cholesterol from macrophages to feces in vivo. Circulation. 2003;108:661-663.
56. Rothblat GH, Phillips MC. High-density lipoprotein heterogeneity and function in reverse cholesterol transport. Curr Opin Lipidol. 2010;21:229-238.
57. Silvennoinen R, Escola-Gil JC, Julve J, Rotllan N, Llaverias G, Metso J, Valledor AF, He J, Yu L, Jauhiainen M, Blanco-Vaca F, Kovanen PT, Lee-Rueckert M. Acute psychological stress accelerates reverse cholesterol transport via corticosterone-dependent inhibition of intestinal cholesterol absorption. Circ Res. 2012;111:1459-1469.
58. Brufau G, Groen AK, Kuipers F. Reverse cholesterol transport revisited: contribution of biliary versus intestinal cholesterol excretion. Arterioscler Thromb Vasc Biol. 2011;31:1726-1733.
59. Turner S, Voogt J, Davidson M, Glass A, Killion S, Decaris J, Mohammed H, Minehira K, Boban D, Murphy E, Luchoomun J, Awada M, Neese R, Hellerstein M. Measurement of reverse cholesterol transport pathways in humans: in vivo rates of free cholesterol effux, esterifcation, and excretion. J Am Heart Assoc. 2012;1:e001826.
60. Yuhanna IS, Zhu Y, Cox BE, Hahner LD, Osborne-Lawrence S, Lu P, Marcel YL, Anderson RG, Mendelsohn ME, Hobbs HH, Shaul PW. High-density lipoprotein binding to scavenger receptor-BI activates endothelial nitric oxide synthase. Nat Med. 2001;7:853-857.
61. Drew BG, Fidge NH, Gallon-Beaumier G, Kemp BE, Kingwell BA. High-density lipoprotein and apolipoprotein AI increase endothelial NO syn-thase activity by protein association and multisite phosphorylation. Proc Natl Acad Sci USA. 2004;101:6999-7004.
62. Kuvin JT, Rämet ME, Patel AR, Pandian NG, Mendelsohn ME, Karas RH. A novel mechanism for the benefcial vascular effects of high-density li-poprotein cholesterol: enhanced vasorelaxation and increased endothelial nitric oxide synthase expression. Am Heart J. 2002;144:165-172.
63. Nicholls SJ, Dusting GJ, Cutri B, Bao S, Drummond GR, Rye KA, Barter PJ. Reconstituted high-density lipoproteins inhibit the acute pro-oxidant and proinfammatory vascular changes induced by a periarterial collar in normocholesterolemic rabbits. Circulation. 2005;111:1543-1550.
64. Viswambharan H, Ming XF, Zhu S, Hubsch A, Lerch P, Vergères G, Rusconi S, Yang Z. Reconstituted high-density lipoprotein inhibits thrombin-induced endothelial tissue factor expression through inhibition of RhoA and stimulation of phosphatidylinositol 3-kinase but not Akt/en-dothelial nitric oxide synthase. Circ Res. 2004;94:918-925.
65. Attie AD, Kastelein JP, Hayden MR. Pivotal role of ABCA1 in reverse cholesterol transport infuencing HDL levels and susceptibility to atherosclerosis. J Lipid Res. 2001;42:1717-1726.
66. Spieker LE, Sudano I, Hürlimann D, Lerch PG, Lang MG, Binggeli C, Corti R, Ruschitzka F, Lüscher TF, Noll G. High-density lipoprotein restores endothelial function in hypercholesterolemic men. Circulation. 2002;105:1399-1402.
67. Sirtori CR, Calabresi L, Franceschini G, Baldassarre D, Amato M, Johansson J, Salvetti M, Monteduro C, Zulli R, Muiesan ML, Agabiti-Rosei E. Cardiovascular status of carriers of the apolipoprotein A-I(Milano) mutant: the Limone sul Garda study. Circulation. 2001;103:1949-1954.
68. 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. Effect of recombinant ApoA-I Milano on coronary atherosclerosis in patients with acute coronary syndromes: a randomized controlled trial. JAMA. 2003;290:2292-2300.
69. Chenevard R, Hürlimann D, Spieker L, Béchir M, Enseleit F, Hermann M, Flammer AJ, Sudano I, Corti R, Lüscher TF, Noll G, Ruschitzka F. Reconstituted HDL in acute coronary syndromes. Cardiovasc Ther. 2012;30:e51-e57.
70. Tardif JC, Grégoire J, L'Allier PL, Ibrahim R, Lespérance J, Heinonen TM, Kouz S, Berry C, Basser R, Lavoie MA, Guertin MC, Rodés-Cabau J; Effect of rHDL on Atherosclerosis-Safety and Effcacy (ERASE) Investigators. Effects of reconstituted high-density lipoprotein infusions on coronary atherosclerosis: a randomized controlled trial. JAMA. 2007;297:1675-1682.
71. Saddar S, Carriere V, Lee WR, Tanigaki K, Yuhanna IS, Parathath S, Morel E, Warrier M, Sawyer JK, Gerard RD, Temel RE, Brown JM, Connelly M, Mineo C, Shaul PW. Scavenger receptor class B type I is a plasma membrane cholesterol sensor. Circ Res. 2013;112:140-151.
72. Nofer JR, van der Giet M, Tölle M, et al. HDL induces NO-dependent vasorelaxation via the lysophospholipid receptor S1P3. J Clin Invest. 2004;113:569-581.
73. Christoffersen C, Obinata H, Kumaraswamy SB, Galvani S, Ahnström J, Sevvana M, Egerer-Sieber C, Muller YA, Hla T, Nielsen LB, Dahlbäck B. Endothelium-protective sphingosine-1-phosphate provided by HDL-associated apolipoprotein M. Proc Natl Acad Sci USA. 2011;108:9613-9618.
74. Nofer JR, Levkau B, Wolinska I, Junker R, Fobker M, von Eckardstein A, Seedorf U, Assmann G. Suppression of endothelial cell apoptosis by high density lipoproteins (HDL) and HDL-associated lysosphingolipids. J Biol Chem. 2001;276:34480-34485.
75. Wilkerson BA, Grass GD, Wing SB, Argraves WS, Argraves KM. Sphingosine 1-phosphate (S1P) carrier-dependent regulation of endo-thelial barrier: high density lipoprotein (HDL)-S1P prolongs endothelial barrier enhancement as compared with albumin-S1P via effects on levels, traffcking, and signaling of S1P1. J Biol Chem. 2012;287:44645-44653.
76. Saddar S, Mineo C, Shaul PW. Signaling by the high-affnity HDL receptor scavenger receptor B type I. Arterioscler Thromb Vasc Biol. 2010;30:144-150.
77. Kimura T, Tomura H, Mogi C, Kuwabara A, Damirin A, Ishizuka T, Sekiguchi A, Ishiwara M, Im DS, Sato K, Murakami M, Okajima F. Role of scavenger receptor class B type I and sphingosine 1-phosphate receptors in high density lipoprotein-induced inhibition of adhesion molecule expression in endothelial cells. J Biol Chem. 2006;281:37457-37467.
78. Tanfn Z, Serrano-Sanchez M, Leiber D. ATP-binding cassette ABCC1 is involved in the release of sphingosine 1-phosphate from rat uterine leiomyoma ELT3 cells and late pregnant rat myometrium. Cell Signal. 2011;23:1997-2004.
79. Navab M, Anantharamaiah GM, Reddy ST, Van Lenten BJ, Ansell BJ, Fogelman AM. Mechanisms of disease: proatherogenic HDL-an evolving feld. Nat Clin Pract Endocrinol Metab. 2006;2:504-511.
80. Keech A, Simes RJ, Barter P, et al; FIELD Study Investigators. Effects of long-term fenofbrate therapy on cardiovascular events in 9795 people with type 2 diabetes mellitus (the FIELD study): randomised controlled trial. Lancet. 2005;366:1849-1861.
81. Bertrand OF, Poirier P, Rodés-Cabau J, Rinfret S, Title LM, Dzavik V, Natarajan M, Angel J, Batalla N, Alméras N, Costerousse O, De Larochellière R, Roy L, Després JP; VICTORY Trial Investigators. Cardiometabolic effects of rosiglitazone in patients with type 2 diabetes and coronary artery bypass grafts: A randomized placebo-controlled clinical trial. Atherosclerosis. 2010;211:565-573.
82. Nissen SE, Wolski K. Effect of rosiglitazone on the risk of myocar-dial infarction and death from cardiovascular causes. N Engl J Med. 2007;356:2457-2471.
83. Home PD, Pocock SJ, Beck-Nielsen H, Gomis R, Hanefeld M, Jones NP, Komajda M, McMurray JJ; RECORD Study Group. Rosiglitazone evaluated for cardiovascular outcomes-an interim analysis. N Engl J Med. 2007;357:28-38.
84. Home PD, Pocock SJ, Beck-Nielsen H, Curtis PS, Gomis R, Hanefeld M, Jones NP, Komajda M, McMurray JJ; RECORD Study Team. Rosiglitazone evaluated for cardiovascular outcomes in oral agent combination therapy for type 2 diabetes (RECORD): a multicentre, randomised, open-label trial. Lancet. 2009;373:2125-2135.
85. Inzucchi SE, Masoudi FA, Wang Y, Kosiborod M, Foody JM, Setaro JF, Havranek EP, Krumholz HM. Insulin-sensitizing antihyperglycemic drugs and mortality after acute myocardial infarction: insights from the National Heart Care Project. Diabetes Care. 2005;28:1680-1689.
86. Masoudi FA, Inzucchi SE, Wang Y, Havranek EP, Foody JM, Krumholz HM. Thiazolidinediones, metformin, and outcomes in older patients with diabetes and heart failure: an observational study. Circulation. 2005;111:583-590.
87. European Medicines Agency. European Medicines Agency recommends suspension of Avandia, Avandamet and Avaglim. Press Release September 23, 2010. http://www.ema.europa.eu/ema/index.jsp?curl=pages/news- and-events/news/2010/09/ news-detail-001119.jsp&murl=menus/news- and-events/news-and-events. jsp&mid=WC0b01ac058004d5c1&jsenabl ed=false.
88. Olsson AG. Laropiprant plus niacin for dyslipidemia and prevention of cardiovascular disease. Expert Opin Pharmacother. 2010;11:1715-1726.
89. Villines TC, Stanek EJ, Devine PJ, Turco M, Miller M, Weissman NJ, Griffen L, Taylor AJ. The ARBITER 6-HALTS Trial (Arterial Biology for the Investigation of the Treatment Effects of Reducing Cholesterol 6-HDL and LDL Treatment Strategies in Atherosclerosis): fnal results and the impact of medication adherence, dose, and treatment duration. J Am Coll Cardiol. 2010;55:2721-2726.
90. HPS2-THRIVE Collaborative Group. HPS2-THRIVE randomized placebo-controlled trial in 25 673 high-risk patients of ER niacin/laropiprant: trial design, pre-specifed muscle and liver outcomes, and reasons for stopping study treatment. Eur Heart J. 2013;34:1279-1291.
91. Landmesser U. The diffcult search for a 'partner' of statins in lipid-targeted prevention of vascular events: the re-emergence and fall of niacin. Eur Heart J. 2013;34:1254-1257.
92. Le Goff W, Guerin M, Chapman MJ. Pharmacological modulation of cholesteryl ester transfer protein, a new therapeutic target in atherogenic dyslipidemia. Pharmacol Ther. 2004;101:17-38.
93. von Eckardstein A. Mulling over the odds of CETP inhibition. Eur Heart J. 2010;31:390-393.
94. Bots ML, Visseren FL, Evans GW, Riley WA, Revkin JH, Tegeler CH, Shear CL, Duggan WT, Vicari RM, Grobbee DE, Kastelein JJ; RADIANCE 2 Investigators. Torcetrapib and carotid intima-media thickness in mixed dyslipidaemia (RADIANCE 2 study): a randomised, double-blind trial. Lancet. 2007;370:153-160.
95. Nissen SE, Tardif JC, Nicholls SJ, Revkin JH, Shear CL, Duggan WT, Ruzyllo W, Bachinsky WB, Lasala GP, Lasala GP, Tuzcu EM; ILLUSTRATE Investigators. Effect of torcetrapib on the progression of coronary atherosclerosis. N Engl J Med. 2007;356:1304-1316.
96. Hu X, Dietz JD, Xia C, Knight DR, Loging WT, Smith AH, Yuan H, Perry DA, Keiser J. Torcetrapib induces aldosterone and cortisol production by an intracellular calcium-mediated mechanism independently of cholester-yl ester transfer protein inhibition. Endocrinology. 2009;150:2211-2219.
97. Forrest MJ, Bloomfeld D, Briscoe RJ, et al. Torcetrapib-induced blood pressure elevation is independent of CETP inhibition and is accompanied by increased circulating levels of aldosterone. Br J Pharmacol. 2008;154:1465-1473.
98. Simic B, Hermann M, Shaw SG, Bigler L, Stalder U, Dörries C, Besler C, Lüscher TF, Ruschitzka F. Torcetrapib impairs endothelial function in hypertension. Eur Heart J. 2012;33:1615-1624.
99. Lüscher TF, Taddei S, Kaski JC, Jukema JW, Kallend D, Münzel T, Kastelein JJ, Deanfeld JE. Vascular effects and safety of dalcetrapib in patients with or at risk of coronary heart disease-the dal-Vessel randomised clinical trial. Eur Heart J. 2012; 33:857-865.
100. Cannon CP, Shah S, Dansky HM, Davidson M, Brinton EA, Gotto AM, Stepanavage M, Liu SX, Gibbons P, Ashraf TB, Zafarino J, Mitchel Y, Barter P; Determining the Effcacy and Tolerability Investigators. Safety of anacetrapib in patients with or at high risk for coronary heart disease. N Engl J Med. 2010;363:2406-2415.
101. Fayad ZA, Mani V, Woodward M, Kallend D, Abt M, Burgess T, Fuster V, Ballantyne CM, Stein EA, Tardif JC, Rudd JH, Farkouh ME, Tawakol A; dal-PLAQUE Investigators. Safety and effcacy of dalcetrapib on atherosclerotic disease using novel non-invasive multi-modality imaging (dal-PLAQUE): a randomised clinical trial. Lancet. 2011;378:1547-1559.
102. Gutstein DE, Krishna R, Johns D, Surks HK, Dansky HM, Shah S, Mitchel YB, Arena J, Wagner JA. Anacetrapib, a novel CETP inhibitor: pursuing a new approach to cardiovascular risk reduction. Clin Pharmacol Ther. 2012;91:109-122.
103. Navab M, Shechter I, Anantharamaiah GM, Reddy ST, Van Lenten BJ, Fogelman AM. Structure and function of HDL mimetics. Arterioscler Thromb Vasc Biol. 2010;30:164-168.
104. Bloedon LT, Dunbar R, Duffy D, Pinell-Salles P, Norris R, DeGroot BJ, Movva R, Navab M, Fogelman AM, Rader DJ. Safety, pharmacokinetics, and pharmacodynamics of oral apoA-I mimetic peptide D-4F in high-risk cardiovascular patients. J Lipid Res. 2008;49:1344-1352.
105. Watson CE, Weissbach N, Kjems L, Ayalasomayajula S, Zhang Y, Chang I, Navab M, Hama S, Hough G, Reddy ST, Soffer D, Rader DJ, Fogelman AM, Schecter A. Treatment of patients with cardiovascular disease with L-4F, an apo-A1 mimetic, did not improve select biomarkers of HDL function. J Lipid Res. 2011;52:361-373.
106. Navab M, Reddy ST, Anantharamaiah GM, Imaizumi S, Hough G, Hama S, Fogelman AM. Intestine may be a major site of action for the apoA-I mimetic peptide 4F whether administered subcutaneously or orally. J Lipid Res. 2011;52:1200-1210.
107. Navab M, Reddy ST, Anantharamaiah GM, Hough G, Buga GM, Danciger J, Fogelman AM. D-4F-mediated reduction in metabolites of arachidonic and linoleic acids in the small intestine is associated with decreased infammation in low-density lipoprotein receptor-null mice. J Lipid Res. 2012;53:437-445.
108. Getz GS, Reardon CA. ApoA-I mimetics: tomatoes to the rescue. J Lipid Res. 2013;54:878-880.
109. Chattopadhyay A, Navab M, Hough G, et al. A novel approach to oral apoA-I mimetic therapy. J Lipid Res. 2013;54:995-1010.
110. Brunham LR, Kruit JK, Iqbal J, Fievet C, Timmins JM, Pape TD, Coburn BA, Bissada N, Staels B, Groen AK, Hussain MM, Parks JS, Kuipers F, Hayden MR. Intestinal ABCA1 directly contributes to HDL biogenesis in vivo. J Clin Invest. 2006;116:1052-1062.
111. Navab M, Reddy ST, Van Lenten BJ, Buga GM, Hough G, Wagner AC, Fogelman AM. High-density lipoprotein and 4F peptide reduce systemic infammation by modulating intestinal oxidized lipid metabolism: novel hypotheses and review of literature. Arterioscler Thromb Vasc Biol. 2012;32:2553-2560.
112. Navab M, Hough G, Buga GM, et al. Transgenic 6F tomatoes act on the small intestine to prevent systemic infammation and dyslipidemia caused by Western diet and intestinally derived lysophosphatidic acid. J Lipid Res. 2013;54:3403-3418.
113. Remaley A. Tomatoes, lysophosphatidic acid, and the small intestine: new pieces in the puzzle of apolipoprotein mimetic peptides? J Lipid Res. 2013;54:3223-3226.
114. Mineo C, Shaul PW. PON-dering differences in HDL function in coronary artery disease. J Clin Invest. 2011;121:2545-2548.