Effect of cholesterol oxides on prostacyclin production and platelet adhesion.
Prostacyclin (PGI2) is synthesized primarily by endothelial cells, is essential for maintenance of vascular integrity, and may play a role in atherogenesis. Human umbilical vein endothelial cells in culture were incubated with either pure cholesterol, 25-hydroxycholesterol, 7-ketocholesterol, cholesterol 5 alpha,6 alpha-epoxide or cholestane-3 beta,5 alpha,6 beta-triol at 10 micrograms/ml culture medium concentration for 12 hours and 24 hours. PGI2 production measured by radioimmunoassay of 6-keto PGF1 alpha, the stable metabolite of PGI2 was inhibited by 39.6%, 27.3%, 40.1% and 31.9% after incubation with 25-hydroxycholesterol, 7-ketocholesterol, cholesterol 5 alpha, 6 alpha-epoxide or cholestane-3 beta,5 alpha,6 beta-triol for 12 hours respectively. Further inhibitory effects were shown after 24 hours of incubation with 25-hydroxycholesterol and 7-ketocholesterol. Platelet adhesion onto endothelial cell monolayers measured by 111In-labeled platelets was enhanced by 104%, 54% and 37% after incubation with cholestane-3 beta, 5 alpha,6 beta-triol, 25-hydroxycholesterol, and 7-ketocholesterol at 10 micrograms/ml concentration for 12 hours respectively. Pure cholesterol at the same concentration had no effect on PGI2 production or platelet adhesion.
Peng
S K
SK
Department of Pathology and Laboratory Medicine, UCLA School of Medicine.
Hu
B
B
Peng
A Y
AY
Morin
R J
RJ
D001161:Arteriosclerosis / Q000139:chemically induced*; D002478:Cells, Cultured; D002784:Cholesterol / Q000737:chemistry / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects*; D011464:Epoprostenol / Q000096:biosynthesis*; D006801:Humans; D010087:Oxides / Q000494:pharmacology*; D010973:Platelet Adhesiveness / Q000187:drug effects*
D010087:Oxides; D002784:Cholesterol; D011464:Epoprostenol