Differential effects on inhibition of cholesterol absorption by plant stanol and plant sterol esters in apoE-/- mice.
OBJECTIVE
'Functional foods' supplemented with plant sterol esters (PSE) and plant stanol esters (PSA) are therapeutic options for the management of hypercholesterolaemia. However, their effects on blood monocytes, endothelial function, atherogenesis, and sterol tissue concentrations are poorly understood.


RESULTS
Male apoE-/- mice (n= 30) were randomized to three different diets for 6 weeks (n= 10 per group): high-cholesterol (1.25%) western-type diet (WTD), WTD + 2% PSE, and WTD + 2% PSA. Both supplements reduced serum cholesterol. WTD + PSE resulted in increased plant sterol serum concentrations and increased inflammatory Ly-6C(high) monocyte numbers. WTD + PSA increased plant stanol serum concentrations and Ly-6C-monocyte numbers, but decreased vascular superoxide release, lipid hydroperoxides, and inflammatory cytokines in aortic tissue, in plasma, and in circulating monocytes. Despite reduced serum cholesterol concentrations, both supplements impaired endothelial vasodilation compared with WTD. WTD + PSA reduced the development of atherosclerotic lesions compared with WTD alone (12.7 ± 3.7 vs. 28.3 ± 3.5%), and WTD + PSE was less effective (17.5 ± 3.7%). WTD + PSE and WTD + PSA reduced the cholesterol content in the liver, but not in the brain. However, WTD + PSE and WTD + PSA increased plant sterol and plant stanol concentrations in the liver as well as in the brain.


CONCLUSIONS
PSE and PSA supplementation reduced serum cholesterol, but increased plant sterol and plant stanol concentrations. Elevated levels of PSE and PSA were associated with endothelial dysfunction and increased central nervous system depositions. Atherosclerotic lesion retardation was more pronounced in WTD + PSA, coinciding with higher regenerative monocyte numbers, decreased oxidative stress, and decreased inflammatory cytokines compared with WTD + PSE.
Klinik für Innere Medizin III, Kardiologie, Angiologie und internistische Intensivmedizin, Universitätsklinikum des Saarlandes, Kirrberger Strasse, Gebäude 40, 66421 Homburg/Saar, Germany. oweingartner@aol.com
Oliver
O
Weingärtner
Christof
C
Ulrich
Dieter
D
Lütjohann
Kenan
K
Ismail
Stephan H
SH
Schirmer
Tim
T
Vanmierlo
Michael
M
Böhm
Ulrich
U
Laufs
D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000378:metabolism; D001057:Apolipoproteins E / Q000172:deficiency / Q000235:genetics; D050197:Atherosclerosis / Q000209:etiology / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control; D002784:Cholesterol / Q000097:blood; D002791:Cholesterol, Dietary / Q000493:pharmacokinetics*; D016207:Cytokines / Q000378:metabolism; D004036:Diet, Atherogenic; D019587:Dietary Supplements / Q000009:adverse effects*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000503:physiopathology; D018836:Inflammation Mediators / Q000378:metabolism; D007408:Intestinal Absorption / Q000187:drug effects; D008054:Lipid Peroxides / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009000:Monocytes / Q000166:cytology / Q000187:drug effects; D009249:NADP / Q000378:metabolism; D010840:Phytosterols / Q000008:administration & dosage* / Q000009:adverse effects* / Q000493:pharmacokinetics; D013481:Superoxides / Q000378:metabolism
D001057:Apolipoproteins E; D002791:Cholesterol, Dietary; D016207:Cytokines; D018836:Inflammation Mediators; D008054:Lipid Peroxides; D010840:Phytosterols; D013481:Superoxides; D009249:NADP; D002784:Cholesterol
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