Cytotoxicity of oxysterols on cultured smooth muscle cells from human umbilical arteries.
The lethal effect of 25- and 26-hydroxycholesterol on smooth muscle cells derived from human umbilical arteries was investigated. The extent of cellular death corresponded with increasing oxysterol concentrations and incubation times. Incubation of the cells with 0.5, 2.5, or 10 micrograms/ml of 25- or 26-hydroxycholesterol revealed a proportionality between the degree of cellular death and oxysterol concentration over the 5 days of the experiment. Correlation coefficients among the degree of cellular death, the exposing period, and oxysterol concentration were significantly different (P < 0.05). However, none of these changes were noted in the smooth muscle cells cultured for 5 days in a medium containing the same concentration of cholesterol or 0.5% ethanol. An increase in the concentration of either serum or cholesterol in the culture medium did not significantly reduce the cytotoxicity of 2.5 micrograms/ml of 26-hydroxycholesterol. The results of this study suggest that oxysterols have an injurious effect on arterial cells, and that the injurious effect could not be altered by cholesterol, which was present at a serum concentration 12 times higher than that of oxysterols.
Zhou
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Department of Food Science, University of Illinois, Urbana 61801.
Smith
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Kummerow
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D016923:Cell Death / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002784:Cholesterol / Q000494:pharmacology*; D004247:DNA / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000494:pharmacology; D006801:Humans; D006888:Hydroxycholesterols / Q000494:pharmacology*; D007700:Kinetics; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects*; D011506:Proteins / Q000378:metabolism; D013997:Time Factors; D014469:Umbilical Arteries / Q000166:cytology / Q000187:drug effects*
D006888:Hydroxycholesterols; D011506:Proteins; C007042:cholest-5-ene-3 beta,26-diol; D000431:Ethanol; C007997:25-hydroxycholesterol; D004247:DNA; D002784:Cholesterol