Arteriosclerosis and Thrombosis, Vol 11, 1287-1294, Copyright © 1991 by American Heart Association

ARTICLES

Sluggish sitosterol turnover and hepatic failure to excrete sitosterol into bile cause expansion of body pool of sitosterol in patients with sitosterolemia and xanthomatosis

AK Bhattacharyya, WE Connor, DS Lin, MM McMurry and RS Shulman
Department of Pathology, Louisiana State University Medical Center, New Orleans 70112.

Sitosterolemia and xanthomatosis are characterized by the development of tendon and tuberous xanthomas at an early age and premature atherosclerosis despite normal plasma cholesterol concentrations. The reason(s) for the xanthoma formation and premature atherosclerosis are not clearly understood. The accumulation of sitosterol in the tissues of these patients could be due to increased uptake of low density lipoprotein (LDL) via LDL receptors because of an expanded sitosterol pool caused by sluggish turnover and decreased excretion of sitosterol into bile and feces coupled with the hyperabsorption of sitosterol. We have studied sitosterol and cholesterol turnovers, the biliary and fecal excretion of neutral and acidic steroids, and the response of plasma sterol (sitosterol and cholesterol) levels to either a sterol- free formula or low plant sterol diet in three patients. The average half-life of the first exponential (tA1/2) for sitosterol was 9.2 +/- 3.3 (mean +/- SD) days, which was more than twice that in normal humans. The second exponential (tB1/2) was 156 +/- 108 days, which was nearly 10 times longer than that for normal humans. The average cholesterol production rate in pool A was 0.87 g/day, which is about 40% of that in normal humans. Cholesterol synthesis measured by the sterol balance technique was also found to be about 70% lower than that for normal humans. In two patients fed a sterol-free formula diet, by 25 days their plasma sitosterol and cholesterol levels had decreased by 42% and 36%, respectively. However, in one patient plasma sitosterol and cholesterol concentrations remained unchanged while on the low plant sterol-mixed food diet.(ABSTRACT TRUNCATED AT 250 WORDS)

This article has been cited by other articles:

				J. E. Wu, F. Basso, R. D. Shamburek, M. J. A. Amar, B. Vaisman, G. Szakacs, C. Joyce, T. Tansey, L. Freeman, B. J. Paigen, et al. Hepatic ABCG5 and ABCG8 Overexpression Increases Hepatobiliary Sterol Transport but Does Not Alter Aortic Atherosclerosis in Transgenic Mice J. Biol. Chem., May 28, 2004; 279(22): 22913 - 22925. [Abstract] [Full Text] [PDF]

				K. Kajinami, M. E. Brousseau, C. Nartsupha, J. M. Ordovas, and E. J. Schaefer ATP binding cassette transporter G5 and G8 genotypes and plasma lipoprotein levels before and after treatment with atorvastatin J. Lipid Res., April 1, 2004; 45(4): 653 - 656. [Abstract] [Full Text] [PDF]

				G. Salen, K. von Bergmann, D. Lutjohann, P. Kwiterovich, J. Kane, S.B. Patel, T. Musliner, P. Stein, B. Musser, and the Multicenter Sitosterolemia Study Group Ezetimibe Effectively Reduces Plasma Plant Sterols in Patients With Sitosterolemia Circulation, March 2, 2004; 109(8): 966 - 971. [Abstract] [Full Text] [PDF]

				L. Yu, K. von Bergmann, D. Lutjohann, H. H. Hobbs, and J. C. Cohen Selective sterol accumulation in ABCG5/ABCG8-deficient mice J. Lipid Res., February 1, 2004; 45(2): 301 - 307. [Abstract] [Full Text] [PDF]

				L. Yu, R. E. Hammer, J. Li-Hawkins, K. von Bergmann, D. Lutjohann, J. C. Cohen, and H. H. Hobbs Disruption of Abcg5 and Abcg8 in mice reveals their crucial role in biliary cholesterol secretion PNAS, December 10, 2002; 99(25): 16237 - 16242. [Abstract] [Full Text] [PDF]

				T Sudhop, Y Sahin, B Lindenthal, C Hahn, C Luers, H K Berthold, and K von Bergmann Comparison of the hepatic clearances of campesterol, sitosterol, and cholesterol in healthy subjects suggests that efflux transporters controlling intestinal sterol absorption also regulate biliary secretion Gut, December 1, 2002; 51(6): 860 - 863. [Abstract] [Full Text] [PDF]

				K. Lu, M.-H. Lee, H. Yu, Y. Zhou, S. A. Sandell, G. Salen, and S. B. Patel Molecular cloning, genomic organization, genetic variations, and characterization of murine sterolin genes Abcg5 and Abcg8 J. Lipid Res., April 1, 2002; 43(4): 565 - 578. [Abstract] [Full Text] [PDF]

				G. Salen, G. Xu, G. S. Tint, A. K. Batta, and S. Shefer Hyperabsorption and retention of campestanol in a sitosterolemic homozygote: comparison with her mother and three control subjects J. Lipid Res., November 1, 2000; 41(11): 1883 - 1889. [Abstract] [Full Text]

				G. M. B. Berger, R. J. Pegoraro, S. B. Patel, P. Naidu, L. Rom, H. Hidaka, A. D. Marais, A. Jadhav, R. P. Naoumova, and G. R. Thompson HMG-CoA reductase is not the site of the primary defect in phytosterolemia J. Lipid Res., May 1, 1998; 39(5): 1046 - 1054. [Abstract] [Full Text]

				S. B. Patel, A. Honda, and G. Salen Sitosterolemia: exclusion of genes involved in reduced cholesterol biosynthesis J. Lipid Res., May 1, 1998; 39(5): 1055 - 1061. [Abstract] [Full Text] [PDF]

				A. Honda, G. Salen, L. B. Nguyen, G. S. Tint, A. K. Batta, and S. Shefer 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 {Delta}7-reductase in liver and mononuclear leukocytes J. Lipid Res., January 1, 1998; 39(1): 44 - 50. [Abstract] [Full Text]