Olive oil and red wine antioxidant polyphenols inhibit endothelial activation: antiatherogenic properties of Mediterranean diet phytochemicals.
OBJECTIVE
Epidemiology suggests that Mediterranean diets are associated with reduced risk of cardiovascular disease. Because monocyte adhesion to the endothelium is crucial in early atherogenesis, we evaluated whether typical olive oil and red wine polyphenols affect endothelial-leukocyte adhesion molecule expression and monocyte adhesion.


RESULTS
Phytochemicals in olive oil and red wine, including oleuropein, hydroxytyrosol, tyrosol, elenolic acid, and resveratrol, with or without antioxidant activity, were incubated with human umbilical vein endothelial cells for 30 minutes, followed by co-incubation with bacterial lipopolysaccharide or cytokines to trigger adhesion molecule expression. At nutritionally relevant concentrations, only oleuropein, hydroxytyrosol, and resveratrol, possessing a marked antioxidant activity, reduced monocytoid cell adhesion to stimulated endothelium, as well as vascular cell adhesion molecule-1 (VCAM-1) mRNA and protein by Northern analysis and cell surface enzyme immunoassay. Reporter gene assays with deletional VCAM-1 promoter constructs indicated the relevance of nuclear factor-kappaB, activator protein-1, and possibly GATA binding sites in mediating VCAM-1 transcriptional inhibition. The involvement of nuclear factor-kappaB and activator protein-1 was finally demonstrated at electrophoretic mobility shift assays.


CONCLUSIONS
Olive oil and red wine antioxidant polyphenols at nutritionally relevant concentrations transcriptionally inhibit endothelial adhesion molecule expression, thus partially explaining atheroprotection from Mediterranean diets.
Carluccio
Maria Annunziata
MA
C.N.R. Institute of Clinical Physiology, Lecce, Italy.
Siculella
Luisa
L
Ancora
Maria Assunta
MA
Massaro
Marika
M
Scoditti
Egeria
E
Storelli
Carlo
C
Visioli
Francesco
F
Distante
Alessandro
A
De Caterina
Raffaele
R
D000818:Animals; D000975:Antioxidants / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D001161:Arteriosclerosis / Q000517:prevention & control*; D002417:Cattle; D002448:Cell Adhesion / Q000187:drug effects; D002478:Cells, Cultured / Q000187:drug effects; D004032:Diet; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism; D005419:Flavonoids / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D057888:Iridoid Glucosides; D039823:Iridoids; D016328:NF-kappa B / Q000378:metabolism; D000069463:Olive Oil; D010636:Phenols / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D010626:Phenylethyl Alcohol / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D010938:Plant Oils / Q000737:chemistry*; D059808:Polyphenols; D011714:Pyrans / Q000737:chemistry / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D000077185:Resveratrol; D013267:Stilbenes / Q000737:chemistry / Q000494:pharmacology; D018808:Transcription Factor AP-1 / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects; D020298:U937 Cells / Q000187:drug effects* / Q000378:metabolism; D019010:Vascular Cell Adhesion Molecule-1 / Q000096:biosynthesis / Q000235:genetics; D014920:Wine / Q000032:analysis*
D000975:Antioxidants; D005419:Flavonoids; D057888:Iridoid Glucosides; D039823:Iridoids; D016328:NF-kappa B; D000069463:Olive Oil; D010636:Phenols; D010938:Plant Oils; D059808:Polyphenols; D011714:Pyrans; D012333:RNA, Messenger; D013267:Stilbenes; D018808:Transcription Factor AP-1; D019010:Vascular Cell Adhesion Molecule-1; C005975:3,4-dihydroxyphenylethanol; C011867:4-hydroxyphenylethanol; C002769:oleuropein; C000352:elenolic acid; D010626:Phenylethyl Alcohol; D000077185:Resveratrol