The effect of carotenoids on the expression of cell surface adhesion molecules and binding of monocytes to human aortic endothelial cells.
Several large epidemiological studies have shown a correlation between elevated plasma carotenoid levels and decreased risk of cardiovascular disease (CVD). One proposed mechanism for the beneficial effect of carotenoids is through functional modulation of potentially atherogenic processes associated with the vascular endothelium. To test this, we incubated confluent human aortic endothelial cell (HAEC) cultures (passages 4-8) for 24 h with each of the five most prevalent carotenoids in human plasma, which are alpha-carotene, beta-carotene, beta-cryptoxanthin, lutein, and lycopene, at an approximate concentration of 1 micromol/l. Carotenoids were solubilized in 0.7% (v/v) tetrahydrofuran and incorporated into FBS before adding to cell culture medium. Due to disparate solubilities in aqueous medium, final concentrations of alpha-carotene, beta-carotene, beta-cryptoxanthin, lutein, and lycopene were 1.7, 1.1, 0.7, 0.9, and 0.3 micromol/l and monolayers accumulated 647, 158, 7, 113, and 9 pmol/mg protein, respectively. Monolayers were then stimulated with IL-1beta (5 ng/ml) for 6 h with subsequent determination of cell surface expression of adhesion molecules as measured by an enzyme-linked immunosorbent assay (ELISA). To assess endothelial cell adhesion to monocytes, IL-1beta-stimulated monolayers were incubated for 10 min with 51Cr-labeled U937 monocytic cells and adhesion determined by isotope counting. Pre-incubation of HAEC with beta-carotene, lutein and lycopene significantly reduced VCAM-1 expression by 29, 28, and 13%, respectively. Pre-incubation with beta-carotene and lutein significantly reduced E-selectin expression by 38 and 34%, respectively. Pre-treatment with beta-carotene, lutein and lycopene significantly reduced the expression of ICAM-1 by 11, 14, and 18%, respectively. While other carotenoids were ineffective, lycopene attenuated both IL-1beta-stimulated and spontaneous HAEC adhesion to U937 monocytic cells by 20 and 25%, respectively. Thus, among the carotenoids, lycopene appears to be most effective in reducing both HAEC adhesion to monocytes and expression of adhesion molecules on the cell surface.
Martin
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Vascular Biology Program, Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, 711 Washington Street, 02111, Boston, MA, USA.
Wu
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Meydani
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D016588:Anticarcinogenic Agents / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology; D001013:Aorta, Thoracic / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D002318:Cardiovascular Diseases / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D002338:Carotenoids / Q000494:pharmacology*; D002448:Cell Adhesion / Q000187:drug effects; D015815:Cell Adhesion Molecules / Q000187:drug effects / Q000378:metabolism*; D065366:Cryptoxanthins; D003470:Culture Media / Q000494:pharmacology; D019040:E-Selectin / Q000187:drug effects / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000187:drug effects / Q000378:metabolism; D007375:Interleukin-1 / Q000494:pharmacology; D014975:Lutein / Q000494:pharmacology; D000077276:Lycopene; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D020298:U937 Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D019010:Vascular Cell Adhesion Molecule-1 / Q000187:drug effects / Q000378:metabolism; D024341:Xanthophylls; D019207:beta Carotene / Q000031:analogs & derivatives / Q000494:pharmacology
D016588:Anticarcinogenic Agents; D000975:Antioxidants; D015815:Cell Adhesion Molecules; D065366:Cryptoxanthins; D003470:Culture Media; D019040:E-Selectin; D007375:Interleukin-1; D019010:Vascular Cell Adhesion Molecule-1; D024341:Xanthophylls; D019207:beta Carotene; D018799:Intercellular Adhesion Molecule-1; D002338:Carotenoids; C041635:alpha-carotene; D000077276:Lycopene; D014975:Lutein