Squalene ameliorates atherosclerotic lesions through the reduction of CD36 scavenger receptor expression in macrophages.
METHODS
Anti-atherogenic features of olive oil (OO) have been attributed, in part, to minor compounds, via diverse mechanisms, although its effects on the CD36 receptor have not been examined. We investigated the effects of minor compounds of OO (squalene (SQ), tyrosol (Tyr) and hydroxytyrosol (OH-Tyr)), on the expression of the CD36 receptor, as well as on monocyte/macrophage differentiation and proliferation.


RESULTS
U937 monocytic cells and macrophages (obtained with 10 nM phorbol-myristate-acetate) were exposed to Tyr, OH-Tyr or SQ at 0, 10, 75 and 200 μM with/without native or oxidised LDL(oxLDL). Flow cytometry was used to achieve the expression of CD36 in both cell types exposed to oxLDL plus antioxidants, as well as the inhibition of monocyte/macrophage differentiation after oxLDL and apoptosis. SQ caused a dose-dependent reduction of CD36 in the presence of native and moderate LDL in monocytes and macrophages. Phenotype-dependent cytotoxic and antiproliferative effects were found for OH-Tyr (p < 0.05), while SQ affected neither monocytes nor macrophages (p < 0.01).


CONCLUSIONS
SQ does not prevent monocyte migration and activation into macrophages, but it would inhibit oxLDL uptake by macrophages, by reducing CD36 expression. This study provides new data about the role of the components of OO in the prevention of atherosclerosis.
Department of Biochemistry and Molecular Biology II, University of Granada, Granada, Spain.
Sergio
S
Granados-Principal
Jose L
JL
Quiles
Cesar L
CL
Ramirez-Tortosa
Julio
J
Ochoa-Herrera
Patricia
P
Perez-Lopez
Mario
M
Pulido-Moran
M Carmen
MC
Ramirez-Tortosa
D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D050197:Atherosclerosis / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D018955:CD36 Antigens / Q000378:metabolism*; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D004353:Drug Evaluation, Preclinical / Q000379:methods; D006801:Humans; D008077:Lipoproteins, LDL / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D009000:Monocytes / Q000187:drug effects / Q000473:pathology; D000069463:Olive Oil; D010626:Phenylethyl Alcohol / Q000031:analogs & derivatives / Q000494:pharmacology; D010938:Plant Oils / Q000737:chemistry; D013185:Squalene / Q000494:pharmacology*; D020298:U937 Cells / Q000187:drug effects
D000975:Antioxidants; D018955:CD36 Antigens; D008077:Lipoproteins, LDL; D000069463:Olive Oil; D010938:Plant Oils; C099252:oxidized low density lipoprotein; C005975:3,4-dihydroxyphenylethanol; C011867:4-hydroxyphenylethanol; D013185:Squalene; D010626:Phenylethyl Alcohol