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A more recent version of this article appeared on December 1, 2006

Papers In Press, published online ahead of print September 6, 2006
J. Lipid Res., doi:10.1194/jlr.M600346-JLR200
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Submitted on July 28, 2006
Revised on August 24, 2006
Accepted on September 5, 2006

Plant sterol or stanol esters, alone or in combination with atorvastatin retard lesion formation in heterozygous LDL receptor deficient mice independent of changes in serum plant sterols

Jogchum Plat, Ilona Beugels, Marion J.J. Gijbels, Menno P.J. de Winther, and Ronald P. Mensink

Human Biology, Maastricht University, Maastricht

Corresponding Author: J.PLAT{at}HB.UNIMAAS.NL

Statins not always lower CHD mortality, which was speculated caused by increased serum plant sterols observed during statin treatment. To evaluate plant sterol atherogenicity we fed LDL-receptor (+/-) mice 35 weeks western diets (control) alone or enriched with atorvastatin, or atorvastatin + plant sterols or stanols. Atorvastatin lowered serum cholesterol by 22% and lesion area by 57%. Adding plant sterols or stanols to atorvastatin lowered serum cholesterol with -39% and -41%. Cholesterol-standardized serum plant sterol concentrations increased 4 to 11-fold during sterol + atorvastatin treatment vs stanol + atorvastatin treatment. However, lesion size decreased similarly in the sterol + atorvastatin (-99% vs control) and the stanol + atorvastatin group (-98%) with comparable serum cholesterol levels, suggesting elevated plant sterol concentrations not being atherogenic. Our 2nd study confirms this conclusion. Compared to lesions after a 33 weeks atherogenic period, lesion size further increased in controls (+97%) during 12 following weeks on diet, while 12 weeks addition of plant sterols or stanols lowered lesion size (66% and 64%). This indicates that in LDLr (+/-) mice (1) elevated cholesterol-standardized serum plant sterol concentrations are not atherogenic, (2) adding plant sterol/stanols to atorvastatin further inhibits lesion formation, and (3) plant sterols/stanols inhibit progression or even induce regression of existing lesions.


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