Phytosterols in cardiovascular disease: Innocuous dietary components, or accelerators of atherosclerosis?

Future Lipidology

Volumn 3, Issue 3, 2008, Pages 301-310

  Jessup, Wendy ^a   Herman, Arnold ^b   Chapman, M John ^c  

^a UNIVERSITY OF NEW SOUTH WALES   (Australia)

^b UNIVERSITY OF ANTWERP   (Belgium)

^c SORBONNE UNIVERSITÉ   (France)

Author keywords

ABC transporters; Atherosclerosis; Campesterol; Cardiovascular disease; Cholesterol; Cholesterol lowering; Ezetimibe; Phytosterol; Phytosterolemia; Sitosterol

Indexed keywords

LOW DENSITY LIPOPROTEIN CHOLESTEROL; PHYTOSTEROL;

ATHEROSCLEROSIS; CARDIOVASCULAR DISEASE; CARDIOVASCULAR RISK; DIET; DIET SUPPLEMENTATION; GENE MUTATION; HUMAN; LIPID ABSORPTION; LIPID BLOOD LEVEL; NONHUMAN; PRIORITY JOURNAL; REVIEW;

ANIMALIA;

EID: 47649115498     PISSN: 17460875     EISSN: None     Source Type: Journal    
DOI: 10.2217/17460875.3.3.301     Document Type: Review

References (80)

1. Moreau RA, Whitaker BD, Hicks KB: Phytosterols, phytostanols, and their conjugates in foods: structural diversity, quantitative analysis, and health-promoting uses. Prog. Lipid Res. 41, 457-500 (2002).
2. Wang DQH: Regulation of intestinal cholesterol absorption. Annu. Rev. Physiol. 69, 221-248 (2007).
3. Altmann SW, Davis HR Jr, Zhu L-J et al.: Niemann-Pick C1 like 1 protein is critical for intestinal cholesterol absorption. Science 303, 1201-1204 (2004).
4. Davis HR Jr, Zhu LJ, Hoos LM et al.: Niemann-Pick C1 like 1 (NPC1L1) is the intestinal phytosterol and cholesterol transporter and a key modulator of whole-body cholesterol homeostasis. J. Biol. Chem. 279, 33586-33592 (2004).
5. Oram JF, Vaughan AM: ATP-binding cassette cholesterol transporters and cardiovascular disease. Circ. Res. 99, 1031-1043 (2006).
6. Berge KE, Tian H, Graf GA et al.: Accumulation of dietary cholesterol in sitosterolemia caused by mutations in adjacent ABC transporters. Science 290, 1771-1775 (2000).
7. Wang J, Sun F, Zhang DW et al.: Sterol transfer by ABCG5 and ABCG8: in vitro assay and reconstitution. J. Biol. Chem. 281, 27894-27904 (2006).
8. Temel RE, Gebre AK, Parks JS, Rudel LL: Compared with acyl-CoA: cholesterol O-acyltransferase (ACAT)1 and lecithin: cholesterol acyltransferase, ACAT2 displays the greatest capacity to differentiate cholesterol from sitosterol. J. Biol. Chem. 278, 47594-47601 (2003).
9. Miettinen TA, Klett EL, Gylling H, Isoniemi H, Patel SB: Liver transplantation in a patient with sitosterolemia and cirrhosis. Gastroenterology 130, 542-547 (2006).
10. Salen G, Shefer S, Nguyen L, Ness GC. Tint GS, Shore V: Sitosterolemia. J. Lipid Res. 33, 945-955 (1992).
11. Salen G, Horak I, Rothkopf M et al.: Lethal atherosclerosis associated with abnormal plasma and tissue sterol composition in sitosterolemia with xanthomatosis. J. Lipid Res. 26, 1126-1133 (1985).
12. Morganroth I Levy RI, McMahon AE, Gotto AM Jr: Pseudohomozygous type II hyperlipoproteinemia. J. Pediatr. 85, 639-643 (1974).
13. Belamarich PF, Deckelbaum RJ, Starc TJ, Dobrin BE, Tint GS, Salen G: Response to diet and cholestyramine in a patient with sitosterolemia. Pediatrics 86, 977-981 (1990).
14. Miettinen TA: Phytosterolaemia, xanthornatosis and premature atherosclerotic arterial disease: a case with high plant sterol absorption, impaired sterol elimination and low cholesterol synthesis. Eur. J. Clin. Invest. 10, 27-35 (1980).
15. Kolovou G, Voudris V, Drogari E, Palatianos G, Cokkinos DV: Coronary bypass grafts in a young girl with sitosterolemia. Eur. Heart J. 17, 965-966 (1996).
16. Bhattacharyya AK, Connor WE: β-sitosterolemia and xanthomatosis. A newly described lipid storage disease in two sisters. J. Clin. Invest. 53, 1033-1043 (1974).
17. Hubacek A Berge KE, Stefkova J et al.: Polymorphisms in ABCG5 and ABCG8 transporters and plasma cholesterol levels. Physiol. Res. 53, 395-401 (2004).
18. Boomsma DI, Princen HM, Frants RR, Gevers Leuven JA, Kempen HJ: Genetic analysis of indicators of cholesterol synthesis and absorption: lathosterol and phytosterols in Dutch twins and their parents. Twin Res. 6, 307-314 (2003).
19. Berge KE, von Bergmann K, Lutjohann D et al.: Heritability of plasma noncholesterol sterols and relationship to DNA sequence polymorphism in ABCG5 and ABCG8. J. Lipid Res. 43, 486-494 (2002).
20. Plat J, Bragt MC, Mensink RP: Common sequence variations in ABCG8 are related to plant sterol metabolism in healthy volunteers. J. Lipid Res. 46, 68-75 (2005).
21. Chan YM, Varady KA, Lin Y et al.: Plasma concentrations of plant sterols: physiology and relationship with coronary heart disease. Nutr. Rev. 64, 385-402 (2006).
22. Gylling H, Miettinen TA: The effect of plant stanol- and sterol-enriched foods on lipid metabolism, serum lipids and coronary heart disease. Ann. Clin. Biochem. 42, 254-263 (2005).
23. Hansel B, Nicolle C, Lalanne F et al.: Effect of low-fat, fermented milk enriched with plant sterols on serum lipid profile and oxidative stress in moderate hypercholesterolemia. Am. J. Clin. Nutr. 86, 790-796 (2007).
24. de Jong A, Plat J, Mensink RP: Metabolic effects of plant sterols and stanols. J. Nutr. Biochem. 14, 362-369 (2003).
25. Nigon F, Serfaty-Lacrosniere C, Beucler I et al.: Plant sterol-enriched margarine lowers plasma LDL In hyperlipidemic subjects with low cholesterol intake: effect of fibrate treatment. Clin. Chein. Lab. Med. 39, 634-640 (2001).
26. Gylling H, Paska P, Vardainen E, Miettinen TA: Serum stemis during stanol ester feeding in a mildly hypercholesterolemic population. J. Lipid Res. 40, 593-600 (1999).
27. Clifton P: Plant sterols and stanols - comparison and contrasts. Sterols versus stanols in cholesterol lowering: is there a difference? Atheroscler: Suppl. 3, 5-9 (2002).
28. Heinemann T, Axtmann G, von Bergmann K: Comparison of intestinal absorption of cholesterol with different plant sterols in man. Eur. J. Clin. Invest. 23, 827-831 (1993).
29. Plat J, Mensink RP: Plant stanol and sterol esters in the control of blood cholesterol levels: mechanism and safety aspects. Am. J. Cardiol. 96, D15-D22 (2005).
30. Santosa S, Varady KA, Abu Mweis S, Jones PJH: Physiological and therapeutic factors affecting cholesterol metabolism: does a reciprocal relationship between cholesterol absorption and synthesis really exist? Life Sci. 80, 505-514 (2007).
31. Miettinen TA, Gylling H, Lindbohm N, Miettinen TE, Rajaratnam RA, Relas H: Serum noncholesterol sterols during inhibition of cholesterol synthesis by statins. J. Lab. Clin. Med. 141, 131-137 (2003).
32. Robinson JG, Davidson MH: Combination therapy with ezetimibe and simvastatin to achieve aggressive LDL reduction. Expert Rev. Cardiovasc. Ther. 4, 461-476 (2006).
33. Miettinen TA, Strandberg TE, Gylling H: Noncholesterol sterols and cholesterol lowering by long-term simvastatin treatment in coronary patients: relation to basal serum cholestanol. Arterioscler. Thromb. Vasc. Biol. 20, 1340-1346 (2000).
34. Miettinen TA, Gylling H: Synthesis and absorption markers of cholesterol in serum and lipoproteins during a large dose of statin treatment. Eur. J. Clin. Invest. 33, 976-982 (2003).
35. Salen G, van Bergmann K, Lutjohann D et al.: Ezetimibe effectively reduces plasma plant sterols in patients with sitosterolemia. Circulation 109, 966-971 (2004).
36. Assmann G, Kannenberg F, Ramey DR, Musliner TA, Gutkin SW, Veltri EP: Effects of ezetimibe, simvastatin, atorvastatin, and ezetimibestatin therapies on non-cholesterol sterols in patients with primary hypercholesterolemia. Curr. Med. Res. Opin. 24, 249-259 (2008).
37. Miettinen TA, Gylling H, Strandberg T, Sarna S: Baseline serum cholestarol as predictor of recurrent coronary events in subgroup of Scandinavian simvastatin survival study. Br. Med. J. 316, 1127-1130 (1998).
38. Assmann G, Cullen P, Erbey J. Ramey DR, Karmenberg F, Schulte H: Plasma sitosterol elevations are associated with an increased incidence of coronary events in men: results of a nested case-control analysis of the Prospective Cardiovascular Munster (PROCAM) study. Nutr Metab. Cardiovasc. Dis. 16, 13-21 (2006).
39. Glueck Cl Speirs J, Tracy T, Stretcher P, Illig E, Vandegrift J: Relationships of serum plant sterols (phytosterols) and cholesterol in 595 hypercholesterolemic subjects, and familial aggregation of phytosterols, cholesterol, and premature coronary heart disease in hyperphytosterolemic probands and their first-degree relatives. Metabolism 40, 842-848 (1991).
40. Sudhop, T, Gottwald BM, von Bergmann K: Serum plant sterols as a potential risk factor for coronary heart disease. Metabolism 51, 1519-1521 (2002).
41. Wilund KR, Yu L, Xu F et al.: No association between plasma levels of plant sterols and atherosclerosis in mice and men. Arterioscler Thromb. Vasc Biol. 24, 2326-2332 (2004).
42. Pinedo S, Vissers MN, von Bergmann K et al.: Plasma levels of plant sterols and the risk of coronary artery disease: the prospective EPIC-Norfolk Population Study. J. Lipid Res. 48, 139-144 (2007).
43. Ntanios FY, van de Kooij AJ, de Deckere EA, Duchateau GS, Trautwein EA: Effects of various amounts of dietary plant sterol esters on plasma and hepatic sterol concentration and aortic foam cell formation of cholesterol-fed hamsters. Atherosclerosis 169, 41-50 (2003).
44. Moghadasian MH, McManus BM, Godin DV, Rodrigues B, Frohlich JJ: Proatherogenic and antiatherogenic effects of probucol and phytosterols in apolipoprotein E-deficient mice: possible mechanisms of action. Circulation 99, 1733-1739 (1999).
45. Volger OL, Mensink RP, Plat J, Hornstra G, Havekes LM, Princen HM: Dietary vegetable oil and wood derived plant stanol esters reduce atherosclerotic lesion size and severity in ApoE*3-Leiden transgenic mice. Atherosclerosis 157, 375-381 (2001).
46. Plat J, Beugels; I, Gijbels MJ, de Winther MP, Mensink RP: Plant sterol or stanol esters retard lesion formation in LDL receptor-deficient mice independent of changes in serum plant sterols. J. Lipid Res. 47, 2762-2771 (2006).
47. Dietschy JM, Turley SD: Control of cholesterol turnover in the mouse. J. Biol. Chem. 277, 3801-3804 (2002).
48. -1 mice and CTX. J. Lipid Res. 42, 291-300 (2001).
49. Simons K, Toomre D: Lipid rafts and signal transduction. Nat. Rev Mol. Cell Biol. 1, 31-39 (2000).
50. Gaus K, Gratton E, Kahle EP et al.: Visualizing lipid structure and raft domains in living cells with two-photon microscopy. Proc. Natl Acad Sci. USA 100, 15554-15559 (2003).
51. Gaus K, Rodriguez M, Ruberu KR et al.: Domain-specific lipid distribution in macrophage plasma membranes. J. Lipid Res. 46, 1526-1538 (2005).
52. Foster LJ, De Hoog CL, Mann M: Unbiased quantitative proteomics of lipid rafts reveals high specificity for signaling factors. Proc. Natl Acad. Sci. USA 100, 5813-5818 (2003).
53. Gaus K, Kritharides L, Schmitz G et al.: Apolipoprotein A-1 interaction with plasma membrane lipid rafts controls cholesterol export from macrophages. FASEB J. 18, 574-576 (2004).
54. Shaul PW: Endothelial nitric oxide synthase, caveolae and the development of atherosclerosis. J Physiol. 547, 21-33 (2003).
55. Xu X, Bittman R, Duportail G, Heissler D, Vilcheze C, London E: Effect of the structure of natural sterols and sphingolipids on the formation of ordered sphingolipid/sterol domains (rafts). Comparison of cholesterol to plant, fungal and disease-associated sterols and comparison of sphingomyelin, cerebrosides and ceramide. J. Biol. Chem. 276, 33540-33546 (2001).
56. Beck JG, Mathieu D, Loudet C, Buchoux S, , Dufourc EJ: Plant sterols in 'rafts': a better way to regulate membrane thermal shocks. FASE J. 21, 1714-1723 (2007).
57. Rujanavech C, Silbert DF: Effect of sterol structure on the partition of sterol between phospholipid vesicles of different composition. J. Biol. Chem. 261, 7215-7219 (1986).
58. Shahedi V, Oradd G, Lindblom G: Domain-formation in DOPC/SM bilayers studied by pfg-NMR: effect of sterol structure. Biophys. J. 91, 2501-2507 (2006).
59. Hac-Wydro K, Wydro P, Jagoda A, Kapusta J: The study on the interaction between phytosterols and phospholipids in model membranes. Chem. Phys. Lipids 150, 22-34 (2007).
60. Rothblat GH, Burns CH: Comparison of the metabolism of cholesterol, cholestanol, and β-sitosterol in L-cell mouse fibroblasts. J. Lipid Res. 12, 653-661 (1971).
61. Connor WE, Lin DS, Pappu AS, Frohlich J, Gerhard G: Dietary sitostanol and campestanol: accumulation in the blood of humans with sitosterolemia and xanthomatosis and in rat tissues. Lipids 40, 919-923 (2005).
62. Miettinen TA, Rallo M, Lepantalo M, Gylling H: Plant sterols in serum and in atherosclerotic plaques of patients undergoing carotid endarterectomy. J. Am. Coll. Caidiol. 45, 1794-1801 (2005).
63. Esfahani M, Soerbo L, Devlin TM: A requirement for cholesterol and its structural features for a human macrophage-like cell line. J. Cell. Biochem. 25, 87-97 (1984).
64. Sato Y, Nishikawa K, Aikawa K et al.: Side-chain structure is critical for the transport of sterols from lysosomes to cytoplasm. Biochim. Biophs. Acta 1257, 38-46 (1995).
65. Suarez Y, Fernandez C, Ledo B et al.: Differential effects of ergosterol and cholesterol on Cdk1 activation and SPE-driven transcription: sterol stringency for cell cycle progression in human cells. Eur. J Biochem. 269, 1761-1771 (2002).
66. Awad AB, Williams H, Fink CS: Effect of phytosterols on cholesterol metabolism and MAP kinase in MDA-MB-231 human breast cancer cells. J. Nutr. Biochem. 14, 111-119 (2003).
67. Adcox C, Boyd L, Oehrl L, Allen J, Fenner G: Comparative effects of phytosterol oxides and cholesterol oxides in cultured macrophage-derived cell lines. J. Agric. Food Chem. 49, 2090-2095 (2001).
68. Bao L, Li Y, Deng S-X, Landry D, Tabas I: Sitosterol-containing lipoproteins trigger free sterol-induced caspase-independent death in ACAT-competent macrophages. J. Biol. Chem. 281, 33635-33649 (2006).
69. Maguire L, Konoplyannikov M, Ford A, Maguire AR, O'Brien NM: Comparison of the cytotoxic effects of β-sitosterol oxides and a cholesterol oxide, 7β-hydroxycholesterol, in cultured mammalian cells. Br. J. Nutr. 90, 767-775 (2003).
70. Li AC, Glass CK: PPAR- and LXR-dependent pathways controlling lipid metabolism and the development of atherosclerosis. J. Lipid Res. 45, 2161-2173 (2004).
71. Bengoechea-Alonso MT, Ericsson J: SREBP in signal transduction: cholesterol metabolism and beyond. Curr. Opin. Cell Biol. 19, 215-222 (2007).
72. Kaneko E, Matsuda M, Yamada Y, Tachibana Y, Shimomura I, Makishima M: Induction of intestinal ATP-binding cassette transporters by a phytosterol-derived liver X receptor agonist. J. Biol. Chem. 278, 36091-36098 (2003).
73. Plat J, Nichols JA, Mensink RP: Plant sterols and stanols: effects on mixed micellar composition and LXR (target gerie) activation. J Lipid Res. 46, 2468-2476 (2005).
74. Yang C, Yu L, Li W, Xu F, Cohen JC, Hobbs HH: Disruption of cholesterol homeostasis by plant sterols. J. Clin. Invest. 114, 813-822 (2004).
75. Vivancos M, Moreno JJ: β-sitosterol modulates antioxidant enzyme response in RAW 264.7 macrophages. Free Radic. Biol. Med. 39, 91-97 (2005).
76. Awad AB, Toczek J, Fink CS: Phytosterols decrease prostaglandin release in cultured P388D1/MAB macrophages. Prostaglandins Leukot. Essent. Fatty Acids 70, 511-520 (2004).
77. Nashed B, Yeganeh B, HayGlass KT, Moghadasian MH: Antiatherogenic effects of dietary plant sterols are associated with inhibition of proinflammatory cytokine production in ApoE-KO mice. J. Nutr. 135, 2438-2444 (2005).
78. Hidaka H, Nakamura T Aoki T et al.: Increased plasma plant sterol levels in heterozygotes with sitosterolemia and xanthomatosis. J. Lipid Res. 31, 881-888 (1990).
79. Davidson MH, Maki KC, Umporowicz DM et al.: Safety and tolerability of esterified phytosterols administered in reduced-fat spread and salad dressing to healthy adult men and women. J. Am. Coll. Nutr. 20, 307-319 (2001).
80. Salen G, Kwiterovich PO Jr, Shefer S et al.: Increased plasma cholestanol and 5 α-saturated plant sterol derivatives in subjects with sitosterolemia and xanthomatosis. J. Lipid Res. 26, 203-209 (1985).