Induction of monocyte differentiation and foam cell formation in vitro by 7-ketocholesterol

摘要: Oxidized LDL (OxLDL) is composed of many potentially proatherogenic molecules, including oxysterols. Of the oxysterols, 7-ketocholesterol (7-KC) found in rela- tively large abundance OxLDL, as well atheroscle- rotic plaque and foam cells vivo. Although there evi- dence that 7-KC activates endothelial cells, its effect on monocytes unknown. We tested hypothesis may induce monocyte differentiation promote cell formation. THP-1 were used a model system treated with over range concen- trations from 0.5 to 10 m g/ml. Changes adhesion properties, morphology, expression antigens characteristic differentiated macrophages moni- tored 7-day period. promoted firmly ad- here display morphologic features macrophages; this was time dose dependent markedly more potent than cholesterol treatment (45% became adherent after 7 days at g/ml vs. less then 5% for control P , 0.01). Similar effects obtained when enriched or OxLDL added cells. 7-KC- expressed CD11b, CD36, CD68, phagocytized latex beads, formed lipid-laden exposure acetylated OxLDL. In con- trast 7-KC, oxysterols known regulatory such 25-hydroxycholesterol, b -hydroxycholesterol, (22 R )-hydroxycholesterol did not effectively differentiation. conclusion, these results demonstrate first prominent oxysterol by peroxidation cholesterol, play an im- portant role promoting These studies also suggest in- duces through sterol-mediated reg- ulatory pathway remains be characterized. —Hayden, J. M., L. Brachova, K. Higgins, Obermiller, A. Sevanian, S. Khandrika, P. D. Reaven. Induction differen- tiation formation vitro 7-ketocholesterol. Lipid Res. 2002. 43: 26-35.