Effect of 25-hydroxycholesterol on cytotoxicity and prostacyclin production in cultured human umbilical arterial endothelial cells.
The effect of cholesterol or 25-hydroxycholesterol on DNA synthesis and prostacyclin synthesis by cultured human umbilical arterial endothelial cells was investigated. Cells incubated with 25-hydroxycholesterol showed an increased rate of cell death, decreased [3H]-thymidine incorporation and increased prostacyclin production as compared to either the control or the pure cholesterol group. 25-hydroxycholesterol caused a concentration- and time-dependent increase in prostacyclin synthesis. The intracellular free calcium concentration of endothelial cells incubated with 25-hydroxycholesterol was markedly increased in a time-dependent manner. Calcium uptake by endothelial cells incubated with 25-hydroxycholesterol for 24 h was markedly increased. It is suggested that 25-hydroxycholesterol may depress DNA synthesis and increase prostacyclin synthesis via an elevation in the intracellular free calcium concentration of endothelial cells.
Kawamura
K
K
Burnsides Research Laboratory, University of Illinois, Urbana 61801.
Kummerow
F A
FA
D002118:Calcium / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D011464:Epoprostenol / Q000096:biosynthesis*; D005456:Fluorescent Dyes; D006801:Humans; D006888:Hydroxycholesterols / Q000494:pharmacology*; D007211:Indoles; D013936:Thymidine / Q000378:metabolism; D014469:Umbilical Arteries / Q000166:cytology / Q000187:drug effects / Q000378:metabolism
D005456:Fluorescent Dyes; D006888:Hydroxycholesterols; D007211:Indoles; C007997:25-hydroxycholesterol; D004247:DNA; D011464:Epoprostenol; C048960:indo-1; D002118:Calcium; D013936:Thymidine