Determinants of plasma HDL concentrations and reverse cholesterol transport

Current Opinion in Cardiology

Volumn 21, Issue 4, 2006, Pages 345-352

  Lewis, Gary F ^a,b  

^a UNIVERSITY OF TORONTO   (Canada)

^b TORONTO GENERAL HOSPITAL   (Canada)

Author keywords

High density lipoprotein; Insulin resistance; Lipase; Lipoprotein; Reverse cholesterol transport

Indexed keywords

HIGH DENSITY LIPOPROTEIN;

ATHEROSCLEROSIS; CELL POPULATION; CHOLESTEROL TRANSPORT; HUMAN; INSULIN RESISTANCE; INTESTINE; LIPID ANALYSIS; LIVER; NONHUMAN; PRIORITY JOURNAL; REVIEW; SURFACE PROPERTY;

APOLIPOPROTEIN A-I; ATHEROSCLEROSIS; ATP-BINDING CASSETTE TRANSPORTERS; CHOLESTEROL, HDL; HUMANS; INSULIN RESISTANCE; LIPASE; MEMBRANE PROTEINS; PHOSPHOLIPID TRANSFER PROTEINS; TRIGLYCERIDES;

EID: 33748194146     PISSN: 02684705     EISSN: None     Source Type: Journal    
DOI: 10.1080/01480540600820387     Document Type: Review

References (73)

1. Glomset JA. The plasma lecithins:cholesterol acyltransferase reaction. J Lipid Res 1968; 9:155-167.
2. Jolley CD, Woollett LA, Turley SD, Dietschy JM. Centripetal cholesterol flux to the liver is dictated by events in the peripheral organs and not by the plasma high density lipoprotein or apolipoprotein A-I concentration. J Lipid Res 1998; 39:2143-2149.
3. 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 2005; 97:763-771. This paper addresses the ongoing debate as to whether the cardioprotective effects of HDL are mediated primarily by direct anti-inflammatory effects of HDL or by reverse cholesterol transport. They show that both are important and that these beneficial effects are independent of plasma HDL cholesterol concentrations.
4. Zhang Y, Zanotti I, Reilly MP, et al. Overexpression of apolipoprotein A-I promotes reverse transport of cholesterol from macrophages to feces in vivo. Circulation 2003; 108:661-663.
5. Zhang Y, Da Silva JR, Reilly M, et al. Hepatic expression of scavenger receptor class B type I (SR-BI) is a positive regulator of macrophage reverse cholesterol transport in vivo. J Clin Invest 2005; 115:2870-2874.
6. Brooks-Wilson A, Marcil M, Clee SM, et al. Mutations in ABC1 in Tangier disease and familial high-density lipoprotein deficiency. Nat Genet 1999; 22:336-345.
7. Lewis GF, Rader DJ. New insights into the regulation of HDL metabolism and reverse cholesterol transport. Circ Res 2005; 96:1221-1232. This comprehensive review of HDL metabolism highlights three insights derived from recent research: (i) the liver is responsible for approximately 80% of plasma HDL concentrations, challenging the concept that cholesterol transport in the body is entirely centripetal from extrahepatic tissues to the liver; (ii) clearance and not production of HDL particles is the major determinant of plasma HDL-C concentration and intravascular modification of HDL particles by lipid exchange, lipolytic modification and receptor interaction all influence particle composition and hence subsequent clearance rates; and (iii) the dominant cause of low plasma HDL-C in humans is the insulin resistance syndrome, with enhanced HDL clearance in this condition being due predominantly to hepatic lipase modification of triglyceride-enriched HDL particles.
8. Srivastava RA, Srivastava N. High density lipoprotein, apolipoprotein A-I, and coronary artery disease. Mol Cell Biochem 2000; 209:131-144.
9. Malik S. Transcriptional regulation of the apolipoprotein AI gene. Front Biosci 2003; 8:d360-d368.
10. Lee JY, Parks JS. ATP-binding cassette transporter AI and its role in HDL formation. Curr Opin Lipidol 2005; 16:19-25.
11. Brinton EA, Eisenberg S, Breslow JL. Increased apo A-I and apo A-II fractional catabolic rate in patients with low high density lipoprotein- cholesterol levels with or without hypertriglyceridemia. J Clin Invest 1991; 87:536-544.
12. Brinton EA, Eisenberg S, Breslow JL. Elevated high density lipoprotein cholesterol levels correlate with decreased apolipoprotein A-I and A-II fractional catabolic rate in women. J Clin Invest 1989; 84:262-269.
13. Brinton EA, Eisenberg S, Breslow JL. Human HDL cholesterol levels are determined by apoA-I fractional catabolic rate, which correlates inversely with estimates of HDL particle size. Effects of gender, hepatic and lipoprotein lipases, triglyceride and insulin levels, and body fat distribution. Arterioscler Thromb 1994; 14:707-720.
14. Horowitz BS, Goldberg IJ, Merab J, et al. Increased plasma and renal clearance of an exchangeable pool of apolipoprotein A-I in subjects with low levels of high density lipoprotein cholesterol. J Clin Invest 1993; 91:1743-1752.
15. Fielding CJ, Fielding PE. Molecular physiology of reverse cholesterol transport. J Lipid Res 1995; 36:211-228.
16. Wolfrum C, Poy MN, Stoffel M. Apolipoprotein M is required for prebeta-HDL formation and cholesterol efflux to HDL and protects against atherosclerosis. Nat Med 2005; 11:418-422. This study highlights the important role of an apolipoprotein that was previously not appreciated to play a role in the formation of pre-β HDL particles. Pre-β HDL particles are efficient cholesterol acceptor particles that play an important role in the initial steps of reverse cholesterol transport.
17. Rotllan N, Ribas V, Calpe-Berdiel L, et al. Overexpression of human apolipoprotein A-II in transgenic mice does not impair macrophage-specific reverse cholesterol transport in vivo. Arterioscler Thromb Vasc Biol 2005; 25:1896.
18. Yancey PG, Bortnick AE, Kellner-Weibel G, et al. Importance of different pathways of cellular cholesterol efflux. Arterioscler Thromb Vasc Biol 2003; 23:712-719.
19. Aiello RJ, Brees D, Bourassa PA, et al. Increased atherosclerosis in hyperlipidemic mice with inactivation of ABCA1 in macrophages. Arterioscler Thromb Vasc Biol 2002; 22:630-637.
20. Van Eck M, Bos IS, Kaminski WE, et al. Leukocyte ABCA1 controls susceptibility to atherosclerosis and macrophage recruitment into tissues. Proc Natl Acad Sci USA 2002; 99:6298-6303.
21. Haghpassand M, Bourassa PA, Francone OL, Aiello RJ. Monocyte/macrophage expression of ABCA1 has minimal contribution to plasma HDL levels. J Clin Invest 2001; 108:1315-1320.
22. 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 2005; 115:1333-1342. By selectively silencing the cholesterol transporter ABCA1 in liver, Timmins et al. demonstrated an approximately 80% reduction in plasma HDL cholesterol and apoAI concentrations, highlighting the important contribution of the liver to the plasma HDL pool.
23. Ragozin S, Niemeier A, Laatsch A, et al. Knockdown of hepatic ABCA1 by RNA interference decreases plasma HDL cholesterol levels and influences postprandial lipemia in mice. Arterioscler Thromb Vasc Biol 2005; 25:1433-1438.
24. Brunham JR, Kruit JK, Iqbal J, et al. Intestinal ABCA1 directly contributes to HDL biogenesis in vivo. J Clin Invest 2006; (in press).
25. Van Eck M, Pennings M, Hoekstra M, et al. Scavenger receptor BI and ATP-binding cassette transporter A1 in reverse cholesterol transport and atherosclerosis. Curr Opin Lipidol 2005; 16:307-315.
26. Wang N, Lan D, Chen W, Matsuura F, Tall AR. ATP-binding cassette transporters G1 and G4 mediate cellular cholesterol efflux to high-density lipoproteins. Proc Natl Acad Sci USA 2004; 101:9774-9779.
27. Kennedy MA, Barrera GC, Nakamura K, et al. ABCG1 has a critical role in mediating cholesterol efflux to HDL and preventing cellular lipid accumulation. Cell Metab 2005; 1:121-131. This study demonstrates an important role for the cholesterol transporter ABCG1 in reverse cholesterol transport, complementing the important function of ABCA1. While ABCA1 mainly transports lipids onto lipid poor apoAI-containing particles, ABCG1 transports cholesterol from the cell membrane to mature HDL.
28. Rothblat GH, Llera-Moya M, Atger V, et al. Cell cholesterol efflux. integration of old and new observations provides new insights. J Lipid Res 1999; 40:781-796.
29. van der Velde AE, Groen AK. Shifting gears: liver SR-BI drives reverse cholesterol transport in macrophages. J Clin Invest 2005; 115:2699-2701.
30. Jonas A. Lecithin cholesterol acyltransferase. Biochim Biophys Acta 2000; 1529:245-256.
31. Nakamura Y, Kotite L, Gan Y, et al. Molecular mechanism of reverse cholesterol transport: reaction of pre-beta-migrating high-density lipoprotein with plasma lecithin/cholesterol acyltransferase. Biochemistry 2004; 43:14811-14820.
32. Barter PJ, Brewer HB Jr, Chapman MJ, et al. Cholesteryl ester transfer protein: a novel target for raising HDL and inhibiting atherosclerosis. Arterioscler Thromb Vasc Biol 2003; 23:160-167.
33. Huuskonen J, Olkkonen VM, Jauhiainen M, Ehnholm C. The impact of phospholipid transfer protein (PLTP) on HDL metabolism. Atherosclerosis 2001; 155:269-281.
34. Merkel M, Eckel RH, Goldberg IJ. Lipoprotein lipase: genetics, lipid uptake, and regulation. J Lipid Res 2002; 43:1997-2006.
35. Guendouzi K, Collet X, Perret B, et al. Remnant high density lipoprotein2 particles produced by hepatic lipase display high-affinity binding and increased endocytosis into a human hepatoma cell line (HEPG2). Biochemistry 1998; 37:14974-14980.
36. Barter PJ. Hugh Sinclair lecture: the regulation and remodelling of HDL by plasma factors. Atheroscler Suppl 2002; 3:39-47.
37. Blades B, Vega GL, Grundy SM. Activities of lipoprotein lipase and hepatic triglyceride lipase in postheparin plasma of patients with low concentrations of HDL cholesterol. Arterioscler Thromb 1993; 13:1227-1235.
38. Lewis GF, Murdoch S, Uffelman K, et al. Hepatic lipase mRNA, protein and plasma enzyme activity is increased in the insulin-resistant fructose-fed Syrian Golden hamster and is partially normalized by the insulin sensitizer, rosiglitazone. Diabetes 2004; 53:2893-2900. This is the first study to examine the expression and activity of hepatic lipase in an animal model made insulin resistant and then insulin sensitized. It showed that hepatic lipase is upregulated in insulin-resistant states and that insulin sensitization partially corrects this upregulation.
39. McCoy MG, Sun GS, Marchadier D, et al. Characterization of the lipolytic activity of endothelial lipase. J Lipid Res 2002; 43:921-929.
40. Maugeais C, Tietge UJ, Broedl UC, et al. Dose-dependent acceleration of high-density lipoprotein catabolism by endothelial lipase. Circulation 2003; 108:2121-2126.
41. Ishida T, Choi S, Kundu RK, et al. Endothelial lipase is a major determinant of HDL level. J Clin Invest 2003; 111:347-355.
42. Jin W, Millar JS, Broedl U, et al. Inhibition of endothelial lipase causes increased HDL cholesterol levels in vivo. J Clin Invest 2003; 111:357-362.
43. Ma K, Cilingiroglu M, Otvos JD, et al. Endothelial lipase is a major genetic determinant for high-density lipoprotein concentration, structure, and metabolism. Proc Natl Acad Sci USA 2003; 100:2748-2753.
44. Murakami M, Kudo I. New phospholipase A(2) isozymes with a potential role in atherosclerosis. Curr Opin Lipidol 2003; 14:431-436.
45. Jin W, Marchadier D, Rader DJ. Lipases and HDL metabolism. Trends Endocrinol Metab 2002; 13:174-178.
46. Tietge UJ, Maugeais C, Lund-Katz S, et al. Human secretory phospholipase A2 mediates decreased plasma levels of HDL cholesterol and apoA-I in response to inflammation in human apoA-I transgenic mice. Arterioscler Thromb Vasc Biol 2002; 22:1213-1218.
47. Trigatti B, Covey S, Rizvi A. Scavenger receptor class B type I in high-density lipoprotein metabolism, atherosclerosis and heart disease: lessons from gene-targeted mice. Biochem Soc Trans 2004; 32:116-120.
48. Trigatti BL, Krieger M, Rigotti A. Influence of the HDL receptor SR-BI on lipoprotein metabolism and atherosclerosis. Arterioscler Thromb Vasc Biol 2003; 23:1732-1738.
49. Webb NR, Cai L, Ziemba KS, et al. The fate of HDL particles in vivo after SR-BI-mediated selective lipid uptake. J Lipid Res 2002; 43:1890-1898.
50. Webb NR, de Beer MC, Asztalos BF, et al. Remodeling of HDL remnants generated by scavenger receptor class B type I. J Lipid Res 2004; 45:1666-1673.
51. de Beer MC, van der Westhuyzen DR, Whitaker NL, et al. SR-BI-mediated selective lipid uptake segregates apoA-I and apoA-II catabolism. J Lipid Res 2005; 46:2143-2150.
52. Gauthier A, Lau P, Zha X, et al. Cholesteryl ester transfer protein directly mediates selective uptake of high density lipoprotein cholesteryl esters by the liver. Arterioscler Thromb Vasc Biol 2005; 25:2177-2184. CETP has traditionally been felt to exert its major action in the exchange of cholesteryl ester between HDL and the apoB-containing lipoproteins or between adipose tissue and lipoproteins. This study demonstrates an important role for CETP in the process of selective cholesterol uptake from HDL by the liver.
53. Fidge NH. High density lipoprotein receptors, binding proteins, and ligands. J Lipid Res 1999; 40:187-201.
54. Steinberg D. A docking receptor for HDL cholesterol esters. Science 1996; 271:460-461.
55. Hammad SM, Barth JL, Knaak C, Argraves WS. Megalin acts in concert with cubilin to mediate endocytosis of high density lipoproteins. J Biol Chem 2000; 275:12003-12008.
56. Hammad SM, Stefansson S, Twal WO, et al. Cubilin, the endocytic receptor for intrinsic factor-vitamin B(12) complex, mediates high-density lipoprotein holoparticle endocytosis. Proc Natl Acad Sci USA 1999; 96:10158-10163.
57. Moestrup SK, Kozyraki R. Cubilin, a high-density lipoprotein receptor. Curr Opin Lipidol 2000; 11:133-140.
58. Despres JP, Lemieux I, Dagenais GR, et al. HDL-Cholesterol as a marker of coronary heart disease risk: the Quebec cardiovascular study. Atherosclerosis 2000; 153:263-272.
59. Rubins HB, Robins SJ, Collins D, et al. Gemfibrozil for the secondary prevention of coronary heart disease in men with low levels of high-density lipoprotein cholesterol. Veterans Affairs High-Density Lipoprotein Cholesterol Intervention Trial Study Group. N Engl J Med 1999; 341:410-418.
60. Vajo Z, Terry JG, Brinton EA. Increased intra-abdominal fat may lower HDL levels by increasing the fractional catabolic rate of A-I in postmenopausal women. Atherosclerosis 2002; 160:495-501.
61. Pont F, Duvillard L, Florentin E, et al. High-density lipoprotein apolipoprotein A-I kinetics in obese insulin resistant patients. An in vivo stable isotope study. Int J Obes Relat Metab Disord 2002; 26:1151-1158.
62. Ji J, Watts GF, Johnson AG, et al. High-density lipoprotein transport in the metabolic syndrome: application of a new model for HDL particle kinetics. J Clin Endocrin Metab 2005 [epub ahead of print].
63. Frenais R, Ouguerram K, Maugeais C, et al. High density lipoprotein apolipoprotein AI kinetics in NIDDM. a stable isotope study. Diabetologia 1997; 40:578-583.
64. Pietzsch J, Julius U, Nitzsche S, Hanefeld M. In vivo evidence for increased apolipoprotein A-I catabolism in subjects with impaired glucose tolerance. Diabetes 1998; 47:1928-1934.
65. Deeb SS, Zambon A, Carr MC, et al. Hepatic lipase and dyslipidemia: interactions among genetic variants, obesity, gender, and diet. J Lipid Res 2003; 44:1279-1286.
66. Lewis GF, Lamarche B, Uffelman KD, et al. Clearance of postprandial and lipolytically-modified human HDL in rabbits and rats. J Lipid Res 1997; 38:1771-1781.
67. Lamarche B, Uffelman KD, Carpentier A, et al. Triglyceride-enrichment of HDL enhances the in vivo metabolic clearance of HDL-apo A-1 in healthy men. J Clin Invest 1999; 103:1191-1199.
68. Rashid S, Uffelman KD, Barrett PHR, et al. Triglyceride enrichment of HDL does not alter selective cholesteryl ester clearance in rabbits. J Lipid Res 2001; 42:265-271.
69. Rashid S, Barrett PH, Uffelman KD, et al. Lipolytically modified triglyceride-enriched HDLs are rapidly cleared from the circulation. Arterioscler Thromb Vasc Biol 2002; 22:483-487.
70. Rashid S, Watanabe T, Sakaue T, Lewis GF. Mechanisms of HDL lowering in insulin resistant, hypertriglyceridemic states: the combined effect of HDL triglyceride enrichment and elevated hepatic lipase activity. Clin Biochem 2003; 36:421-429.
71. Rashid S, Trinh DK, Uffelman KD, et al. Expression of human hepatic lipase in the rabbit model preferentially enhances the clearance of triglyceride-enriched versus native high-density lipoprotein apolipoprotein A-I. Circulation 2003; 107:3066-3072.
72. Reilly MP, Rader DJ. The metabolic syndrome: more than the sum of its parts? Circulation 2003; 108:1546-1551.
73. Broedl UC, Jin W, Rader DJ. Endothelial lipase: a modulator of lipoprotein metabolism upregulated by inflammation. Trends Cardiovasc Med 2004; 14:202-206.