Non-cholesterol sterols and cholesterol metabolism in sitosterolemia

Atherosclerosis

Volumn 231, Issue 2, 2013, Pages 291-299

  Othman, Rgia A ^a,b   Myrie, Semone B ^a,b   Jones, Peter J H ^a,b  

^a UNIVERSITY OF MANITOBA   (Canada)

^b UNIVERSITY OF MANITOBA   (Canada)

Author keywords

ABCG5 8; Atherosclerosis; Cholesterol; HMG CoA reductase; Non cholesterol sterols; NPC1L1; Plant sterols; SOAT2; Xanthoma

Indexed keywords

BIOLOGICAL MARKER; BRASSICASTEROL; CAMPESTANOL; CAMPESTEROL; CHOLESTEROL; EZETIMIBE; NPC1L1 PROTEIN; PHYTOSTEROL; SITOSTANOL; SITOSTEROL; STANOL ESTER; STANOZOLOL; STIGMASTEROL; UNCLASSIFIED DRUG;

ATHEROSCLEROSIS; AUTOSOMAL RECESSIVE DISORDER; CHEMICAL STRUCTURE; CHOLESTEROL BLOOD LEVEL; CHOLESTEROL METABOLISM; CHOLESTEROL SYNTHESIS; DIETARY INTAKE; HUMAN; INTESTINE ABSORPTION; LIPID ABSORPTION; PRIORITY JOURNAL; REVIEW; SITOSTEROLEMIA; STEROL METABOLISM; XANTHOMA;

ABCG5/8; ATHEROSCLEROSIS; CHOLESTEROL; HMG COA REDUCTASE; NON-CHOLESTEROL STEROLS; NPC1L1; PLANT STEROLS; SOAT2; XANTHOMA;

ABSORPTION; ATHEROSCLEROSIS; ATP-BINDING CASSETTE TRANSPORTERS; AZETIDINES; CHOLESTEROL; DISEASE PROGRESSION; HUMANS; HYPERCHOLESTEROLEMIA; INTESTINAL DISEASES; KINETICS; LIPID METABOLISM, INBORN ERRORS; MEMBRANE PROTEINS; PHYTOSTEROLS; SITOSTEROLS; STEROL O-ACYLTRANSFERASE; STEROLS; XANTHOMATOSIS;

EID: 84888175640     PISSN: 00219150     EISSN: 18791484     Source Type: Journal    
DOI: 10.1016/j.atherosclerosis.2013.09.038     Document Type: Review

References (105)

1. Salen G., Shefer S., Nguyen L., Ness G.C., Tint G.S., Shore V. Sitosterolemia. JLipid Res 1992, 33:945-955.
2. Bhattacharyya A.K., Connor W.E. Beta-sitosterolemia and xanthomatosis. A newly described lipid storage disease in two sisters. JClin Invest 1974, 53:1033-1043.
3. Miettinen T.A. Phytosterolaemia, xanthomatosis and premature atherosclerotic arterial disease: a case with high plant sterol absorption, impaired sterol elimination and low cholesterol synthesis. Eur J Clin Invest 1980, 10:27-35.
4. Neff A.T. Sitosterolemia's stomatocytosis and macrothrombocytopenia. Blood 2012, 120:4283.
5. Berger G.M., Deppe W.M., Marais A.D., Biggs M. Phytosterolaemia in three unrelated South African families. Postgrad Med J 1994, 70:631-637.
6. Wang G., Cao L., Wang Z., et al. Macrothrombocytopenia/stomatocytosis specially associated with phytosterolemia. Clin Appl Thromb Hemost 2012, 18:582-587.
7. Wang G., Wang Z., Liang J., Cao L., Bai X., Ruan C. Aphytosterolemia patient presenting exclusively with macrothrombocytopenia and stomatocytic hemolysis. Acta Haematol 2011, 126:95-98.
8. Skrede B., Bjorkhem I., Bergesen O., Kayden H.J., Skrede S. The presence of 5 alpha-sitostanol in the serum of a patient with phytosterolemia, and its biosynthesis from plant steroids in rats with bile fistula. Biochim Biophys Acta 1985, 836:368-375.
9. Su Y., Wang Z., Yang H., et al. Clinical and molecular genetic analysis of a family with sitosterolemia and co-existing erythrocyte and platelet abnormalities. Haematologica 2006, 91:1392-1395.
10. Kidambi S., Patel S.B. Sitosterolaemia: pathophysiology, clinical presentation and laboratory diagnosis. JClin Pathol 2008, 61:588-594.
11. Kolovou G., Voudris V., Drogari E., Palatianos G., Cokkinos D.V. Coronary bypass grafts in a young girl with sitosterolemia. Eur Heart J 1996, 17:965-966.
12. Rees D.C., Iolascon A., Carella M., et al. Stomatocytic haemolysis and macrothrombocytopenia (Mediterranean stomatocytosis/macrothrombocytopenia) is the haematological presentation of phytosterolaemia. Br J Haematol 2005, 130:297-309.
13. Solca C., Tint G.S., Patel S.B. Dietary xenosterols lead to infertility and loss of abdominal adipose tissue in sterolin-deficient mice. JLipid Res 2013, 54:397-409.
14. Mushtaq T., Wales J.K., Wright N.P. Adrenal insufficiency in phytosterolaemia. Eur J Endocrinol 2007, 157(Suppl.1):S61-S65.
15. Mannucci L., Guardamagna O., Bertucci P., et al. Beta-sitosterolaemia: a new nonsense mutation in the ABCG5 gene. Eur J Clin Invest 2007, 37:997-1000.
16. Honda A., Salen G., Nguyen L.B., Tint G.S., Batta A.K., Shefer S. Down-regulation of cholesterol biosynthesis in sitosterolemia: diminished activities of acetoacetyl-CoA thiolase, 3-hydroxy-3-methylglutaryl-CoA synthase, reductase, squalene synthase, and 7-dehydrocholesterol delta7-reductase in liver and mononuclear leukocytes. JLipid Res 1998, 39:44-50.
17. Gregg R.E., Connor W.E., Lin D.S., Brewer H.B. Abnormal metabolism of shellfish sterols in a patient with sitosterolemia and xanthomatosis. JClin Invest 1986, 77:1864-1872.
18. Patel M.D., Thompson P.D. Phytosterols and vascular disease. Atherosclerosis 2006, 186:12-19.
19. Heinemann T., Axtmann G., von Bergmann K. Comparison of intestinal absorption of cholesterol with different plant sterols in man. Eur J Clin Invest 1993, 23:827-831.
20. Bradford P.G., Awad A.B. Phytosterols as anticancer compounds. Mol Nutr Food Res 2007, 51:161-170.
21. Connor W.E., Lin D.S. Absorption and transport of shellfish sterols in human subjects. Gastroenterology 1981, 81:276-284.
22. Lutjohann D., Bjorkhem I., Ose L. Phytosterolaemia in a Norwegian family: diagnosis and characterization of the first Scandinavian case. Scand J Clin Lab Invest 1996, 56:229-240.
23. Armstrong M.J., Carey M.C. Thermodynamic and molecular determinants of sterol solubilities in bile salt micelles. JLipid Res 1987, 28:1144-1155.
24. Hassan A.S., Rampone A.J. Intestinal absorption and lymphatic transport of cholesterol and beta-sitostanol in the rat. JLipid Res 1979, 20:646-653.
25. Hamada T., Goto H., Yamahira T., Sugawara T., Imaizumi K., Ikeda I. Solubility in and affinity for the bile salt micelle of plant sterols are important determinants of their intestinal absorption in rats. Lipids 2006, 41:551-556.
26. Miettinen T.A., Vuoristo M., Nissinen M., Jarvinen H.J., Gylling H. Serum, biliary, and fecal cholesterol and plant sterols in colectomized patients before and during consumption of stanol ester margarine. Am J Clin Nutr 2000, 71:1095-1102.
27. Lee R.G., Willingham M.C., Davis M.A., Skinner K.A., Rudel L.L. Differential expression of ACAT1 and ACAT2 among cells within liver, intestine, kidney, and adrenal of nonhuman primates. JLipid Res 2000, 41:1991-2001.
28. Temel R.E., Gebre A.K., Parks J.S., Rudel L.L. Compared with acyl-CoA:cholesterol O-acyltransferase (ACAT) 1 and lecithin:cholesterol acyltransferase, ACAT2 displays the greatest capacity to differentiate cholesterol from sitosterol. JBiol Chem 2003, 278:47594-47601.
29. Graf G.A., Li W.P., Gerard R.D., et al. Coexpression of ATP-binding cassette proteins ABCG5 and ABCG8 permits their transport to the apical surface. JClin Invest 2002, 110:659-669.
30. Berge K.E., Tian H., Graf G.A., et al. Accumulation of dietary cholesterol in sitosterolemia caused by mutations in adjacent ABC transporters. Science 2000, 290:1771-1775.
31. Izar M.C., Tegani D.M., Kasmas S.H., Fonseca F.A. Phytosterols and phytosterolemia: gene-diet interactions. Genes Nutr 2011, 6:17-26.
32. van der Wulp M.Y., Verkade H.J., Groen A.K. Regulation of cholesterol homeostasis. Mol Cell Endocrinol 2013, 368:1-16.
33. Jia L., Betters J.L., Yu L. Niemann-pick C1-like 1 (NPC1L1) protein in intestinal and hepatic cholesterol transport. Annu Rev Physiol 2011, 73:239-259.
34. Field F.J., Born E., Mathur S.N. LXR/RXR ligand activation enhances basolateral efflux of beta-sitosterol in CaCo-2 cells. JLipid Res 2004, 45:905-913.
35. Abumrad N.A., Davidson N.O. Role of the gut in lipid homeostasis. Physiol Rev 2012, 92:1061-1085.
36. Rios J., Stein E., Shendure J., Hobbs H.H., Cohen J.C. Identification by whole-genome resequencing of gene defect responsible for severe hypercholesterolemia. Hum Mol Genet 2010, 19:4313-4318.
37. Salen G., Shore V., Tint G.S., et al. Increased sitosterol absorption, decreased removal, and expanded body pools compensate for reduced cholesterol synthesis in sitosterolemia with xanthomatosis. JLipid Res 1989, 30:1319-1330.
38. Yoshida A., Naito M., Miyazaki K. Japanese sisters associated with pseudohomozygous familial hypercholesterolemia and sitosterolemia. JAtheroscler Thromb 2000, 7:33-38.
39. Beaty T.H., Kwiterovich P.O., Khoury M.J., et al. Genetic analysis of plasma sitosterol, apoprotein B, and lipoproteins in a large Amish pedigree with sitosterolemia. Am J Hum Genet 1986, 38:492-504.
40. Kwiterovich P.O., Bachorik P.S., Smith H.H., et al. Hyperapobetalipoproteinaemia in two families with xanthomas and phytosterolaemia. Lancet 1981, 1:466-469.
41. Masana L., Joven J., Rubies-Prat J., Lewis B. Low density lipoprotein metabolism and receptor studies in a patient with pseudohomozygous familial hypercholesterolaemia. Acta Paediatr Scand 1990, 79:475-476.
42. Brown M.S., Goldstein J.L. The SREBP pathway: regulation of cholesterol metabolism by proteolysis of a membrane-bound transcription factor. Cell 1997, 89:331-340.
43. Patel S.B., Honda A., Salen G. Sitosterolemia: exclusion of genes involved in reduced cholesterol biosynthesis. JLipid Res 1998, 39:1055-1061.
44. Bhattacharyya A.K., Connor W.E., Lin D.S., McMurry M.M., Shulman R.S. Sluggish sitosterol turnover and hepatic failure to excrete sitosterol into bile cause expansion of body pool of sitosterol in patients with sitosterolemia and xanthomatosis. Arterioscler Thromb 1991, 11:1287-1294.
45. Connor W.E., Lin D.S., Pappu A.S., Frohlich J., Gerhard G. Dietary sitostanol and campestanol: accumulation in the blood of humans with sitosterolemia and xanthomatosis and in rat tissues. Lipids 2005, 40:919-923.
46. Salen G., Kwiterovich P.O., Shefer S., et al. Increased plasma cholestanol and 5 alpha-saturated plant sterol derivatives in subjects with sitosterolemia and xanthomatosis. JLipid Res 1985, 26:203-209.
47. Salen G., Xu G., Tint G.S., Batta A.K., Shefer S. Hyperabsorption and retention of campestanol in a sitosterolemic homozygote: comparison with her mother and three control subjects. JLipid Res 2000, 41:1883-1889.
48. Hidaka H., Nakamura T., Aoki T., et al. Increased plasma plant sterol levels in heterozygotes with sitosterolemia and xanthomatosis. JLipid Res 1990, 31:881-888.
49. Salen G., Tint G.S., Shefer S., Shore V., Nguyen L. Increased sitosterol absorption is offset by rapid elimination to prevent accumulation in heterozygotes with sitosterolemia. Arterioscler Thromb 1992, 12:563-568.
50. Myrie S.B., Mymin D., Triggs-Raine B., Jones P.J. Serum lipids, plant sterols, and cholesterol kinetic responses to plant sterol supplementation in phytosterolemia heterozygotes and control individuals. Am J Clin Nutr 2012, 95:837-844.
51. Brown J.M., Rudel L.L., Yu L. NPC1L1 (Niemann-Pick C1-like 1) mediates sterol-specific unidirectional transport of non-esterified cholesterol in McArdle-RH7777 hepatoma cells. Biochem J 2007, 406:273-283.
52. Yamanashi Y., Takada T., Suzuki H. Niemann-Pick C1-like 1 overexpression facilitates ezetimibe-sensitive cholesterol and beta-sitosterol uptake in CaCo-2 cells. JPharmacol Exp Ther 2007, 320:559-564.
53. Zhang J.H., Ge L., Qi W., et al. The N-terminal domain of NPC1L1 protein binds cholesterol and plays essential roles in cholesterol uptake. JBiol Chem 2011, 286:25088-25097.
54. Kwon H.J., Palnitkar M., Deisenhofer J. The structure of the NPC1L1 N-terminal domain in a closed conformation. PLoS One 2011, 6:e18722.
55. Nguyen T.M., Sawyer J.K., Kelley K.L., Davis M.A., Kent C.R., Rudel L.L. ACAT2 and ABCG5/G8 are both required for efficient cholesterol absorption in mice: evidence from thoracic lymph duct cannulation. JLipid Res 2012, 53:1598-1609.
56. Tang W., Ma Y., Jia L., Ioannou Y.A., Davies J.P., Yu L. Genetic inactivation of NPC1L1 protects against sitosterolemia in mice lacking ABCG5/ABCG8. JLipid Res 2009, 50:293-300.
57. Salen G., von Bergmann K., Lutjohann D., et al. Ezetimibe effectively reduces plasma plant sterols in patients with sitosterolemia. Circulation 2004, 109:966-971.
58. Miettinen T.A., Tilvis R.S., Kesaniemi Y.A. Serum plant sterols and cholesterol precursors reflect cholesterol absorption and synthesis in volunteers of a randomly selected male population. Am J Epidemiol 1990, 131:20-31.
59. Yang C., McDonald J.G., Patel A., et al. Sterol intermediates from cholesterol biosynthetic pathway as liver X receptor ligands. JBiol Chem 2006, 281:27816-27826.
60. Lutjohann D., Bjorkhem I., Beil U.F., von Bergmann K. Sterol absorption and sterol balance in phytosterolemia evaluated by deuterium-labeled sterols: effect of sitostanol treatment. JLipid Res 1995, 36:1763-1773.
61. Yu L., von Bergmann K., Lutjohann D., Hobbs H.H., Cohen J.C. Selective sterol accumulation in ABCG5/ABCG8-deficient mice. JLipid Res 2004, 45:301-307.
62. Yang C., Yu L., Li W., Xu F., Cohen J.C., Hobbs H.H. Disruption of cholesterol homeostasis by plant sterols. JClin Invest 2004, 114:813-822.
63. Wang H.H., Patel S.B., Carey M.C., Wang D.Q. Quantifying anomalous intestinal sterol uptake, lymphatic transport, and biliary secretion in Abcg8(-/-) mice. Hepatology 2007, 45:998-1006.
64. Nguyen L.B., Shefer S., Salen G., et al. Amolecular defect in hepatic cholesterol biosynthesis in sitosterolemia with xanthomatosis. JClin Invest 1990, 86:923-931.
65. Nguyen L.B., Salen G., Shefer S., Tint G.S., Ruiz F. Macrophage 3-hydroxy-3-methylglutaryl coenzyme a reductase activity in sitosterolemia: effects of increased cellular cholesterol and sitosterol concentrations. Metabolism 2001, 50:1224-1229.
66. Fernandez C., Suarez Y., Ferruelo A.J., Gomez-Coronado D., Lasuncion M.A. Inhibition of cholesterol biosynthesis by delta22-unsaturated phytosterols via competitive inhibition of sterol delta24-reductase in mammalian cells. Biochem J 2002, 366:109-119.
67. Sharpe R.L., Drolet M., MacLatchy D.L. Investigation of de novo cholesterol synthetic capacity in the gonads of goldfish (Carassius auratus) exposed to the phytosterol beta-sitosterol. Reprod Biol Endocrinol 2006, 4:60.
68. Ho S.S., Pal S. Margarine phytosterols decrease the secretion of atherogenic lipoproteins from HepG2 liver and Caco2 intestinal cells. Atherosclerosis 2005, 182:29-36.
69. Park Y., Carr T.P. Unsaturated fatty acids and phytosterols regulate cholesterol transporter genes in Caco-2 and HepG2 cell lines. Nutr Res 2013, 33:154-161.
70. Rosenblat M., Volkova N., Aviram M. Pomegranate phytosterol (beta-sitosterol) and polyphenolic antioxidant (punicalagin) addition to statin, significantly protected against macrophage foam cells formation. Atherosclerosis 2013, 226:110-117.
71. Honda A., Salen G., Honda M., et al. 3-Hydroxy-3-methylglutaryl-coenzyme A reductase activity is inhibited by cholesterol and up-regulated by sitosterol in sitosterolemic fibroblasts. JLab Clin Med 2000, 135:174-179.
72. Mymin D., Wang J., Frohlich J., Hegele R.A. Image in cardiovascular medicine. Aortic xanthomatosis with coronary ostial occlusion in a child homozygous for a nonsense mutation in ABCG8. Circulation 2003, 107:791.
73. Braamskamp M.J., Wijburg F.A., Wiegman A. Drug therapy of hypercholesterolaemia in children and adolescents. Drugs 2012, 72:759-772.
74. Cheng W.F., Yuen Y.P., Chow C.B., Au K.M., Chan Y.W., Tam S.C. Sitosterolaemia and xanthomatosis in a child. Hong Kong Med J 2003, 9:206-209.
75. Miettinen T.A., Klett E.L., Gylling H., Isoniemi H., Patel S.B. Liver transplantation in a patient with sitosterolemia and cirrhosis. Gastroenterology 2006, 130:542-547.
76. Salen G., Horak I., Rothkopf M., et al. Lethal atherosclerosis associated with abnormal plasma and tissue sterol composition in sitosterolemia with xanthomatosis. JLipid Res 1985, 26:1126-1133.
77. Sabeva N.S., McPhaul C.M., Li X., Cory T.J., Feola D.J., Graf G.A. Phytosterols differentially influence ABC transporter expression, cholesterol efflux and inflammatory cytokine secretion in macrophage foam cells. JNutr Biochem 2011, 22:777-783.
78. Falk E., Shah P.K., Fuster V. Coronary plaque disruption. Circulation 1995, 92:657-671.
79. 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. JBiol Chem 2006, 281:33635-33649.
80. Rubis B., Paszel A., Kaczmarek M., Rudzinska M., Jelen H., Rybczynska M. Beneficial or harmful influence of phytosterols on human cells?. Br J Nutr 2008, 100:1183-1191.
81. Plat J., Brzezinka H., Lutjohann D., Mensink R.P., von Bergmann K. Oxidized plant sterols in human serum and lipid infusions as measured by combined gas-liquid chromatography-mass spectrometry. JLipid Res 2001, 42:2030-2038.
82. Weingartner O., Ulrich C., Lutjohann D., et al. Differential effects on inhibition of cholesterol absorption by plant stanol and plant sterol esters in apoE-/- mice. Cardiovasc Res 2011, 90:484-492.
83. Carvalho J.F., Silva M.M., Moreira J.N., Simoes S., Sá e Melo M.L. Sterols as anticancer agents: synthesis of ring-B oxygenated steroids, cytotoxic profile, and comprehensive SAR analysis. JMed Chem 2010, 53:7632-7638.
84. Ntanios F.Y., Jones P.J., Frohlich J.J. Dietary sitostanol reduces plaque formation but not lecithin cholesterol acyl transferase activity in rabbits. Atherosclerosis 1998, 138:101-110.
85. Weingartner O., Lutjohann D., Ji S., et al. Vascular effects of diet supplementation with plant sterols. JAm Coll Cardiol 2008, 51:1553-1561.
86. McDaniel A.L., Alger H.M., Sawyer J.K., et al. Phytosterol feeding causes toxicity in ABCG5/G8 knockout mice. Am J Pathol 2013, 182:1131-1138.
87. Wilund K.R., Yu L., Xu F., et al. No association between plasma levels of plant sterols and atherosclerosis in mice and men. Arterioscler Thromb Vasc Biol 2004, 24:2326-2332.
88. Othman R.A., Moghadasian M.H. Beyond cholesterol-lowering effects of plant sterols: clinical and experimental evidence of anti-inflammatory properties. Nutr Rev 2011, 69:371-382.
89. Genser B., Silbernagel G., De Backer G., et al. Plant sterols and cardiovascular disease: a systematic review and meta-analysis. Eur Heart J 2012, 33:444-451.
90. Tsubakio-Yamamoto K., Nishida M., Nakagawa-Toyama Y., Masuda D., Ohama T., Yamashita S. Current therapy for patients with sitosterolemia - effect of ezetimibe on plant sterol metabolism. JAtheroscler Thromb 2010, 17:891-900.
91. Alam M., Garzon M.C., Salen G., Starc T.J. Tuberous xanthomas in sitosterolemia. Pediatr Dermatol 2000, 17:447-449.
92. Parsons H.G., Jamal R., Baylis B., Dias V.C., Roncari D. Amarked and sustained reduction in LDL sterols by diet and cholestyramine in beta-sitosterolemia. Clin Invest Med 1995, 18:389-400.
93. Cobb M.M., Salen G., Tint G.S., Greenspan J., Nguyen L.B. Sitosterolemia: opposing effects of cholestyramine and lovastatin on plasma sterol levels in a homozygous girl and her heterozygous father. Metabolism 1996, 45:673-679.
94. Nguyen L., Salen G., Shefer S., Shore V., Tint G.S., Ness G. Unexpected failure of bile acid malabsorption to stimulate cholesterol synthesis in sitosterolemia with xanthomatosis. Comparison with lovastatin. Arteriosclerosis 1990, 10:289-297.
95. Nguyen L.B., Cobb M., Shefer S., Salen G., Ness G.C., Tint G.S. Regulation of cholesterol biosynthesis in sitosterolemia: effects of lovastatin, cholestyramine, and dietary sterol restriction. JLipid Res 1991, 32:1941-1948.
96. Belamarich P.F., Deckelbaum R.J., Starc T.J., Dobrin B.E., Tint G.S., Salen G. Response to diet and cholestyramine in a patient with sitosterolemia. Pediatrics 1990, 86:977-981.
97. Niu D.M., Chong K.W., Hsu J.H., et al. Clinical observations, molecular genetic analysis, and treatment of sitosterolemia in infants and children. JInherit Metab Dis 2010, 33:437-443.
98. Lutjohann D., von Bergmann K., Sirah W., et al. Long-term efficacy and safety of ezetimibe 10 mg in patients with homozygous sitosterolemia: a 2-year, open-label extension study. Int J Clin Pract 2008, 62:1499-1510.
99. Musliner T., Cselovszky D., Sirah W., et al. Efficacy and safety of ezetimibe 40mg vs. ezetimibe 10mg in the treatment of patients with homozygous sitosterolaemia. Int J Clin Pract 2008, 62:995-1000.
100. Wang J., Joy T., Mymin D., Frohlich J., Hegele R.A. Phenotypic heterogeneity of sitosterolemia. JLipid Res 2004, 45:2361-2367.
101. Salen G., Starc T., Sisk C.M., Patel S.B. Intestinal cholesterol absorption inhibitor ezetimibe added to cholestyramine for sitosterolemia and xanthomatosis. Gastroenterology 2006, 130:1853-1857.
102. Patel A.Y., Pillarisetti J., Marr J., Vacek J.L. Ezetimibe in combination with a statin does not reduce all-cause mortality. JClin Med Res 2013, 5:275-280.
103. O'Callaghan Y., Kenny O., O'Connell N.M., Maguire A.R., McCarthy F.O., O'Brien N.M. Synthesis and assessment of the relative toxicity of the oxidised derivatives of campesterol and dihydrobrassicasterol in U937 and HepG2 cells. Biochimie 2013, 95:496-503.
104. Daly T.J., Aherne S.A., O'Connor T.P., O'Brien N.M. Lack of genoprotective effect of phytosterols and conjugated linoleic acids on Caco-2 cells. Food Chem Toxicol 2009, 47:1791-1796.
105. Katayama T., Satoh T., Yagi T., et al. A19-year-old man with myocardial infarction and sitosterolemia. Intern Med 2003, 42:591-594.