Document Detail

Induction of monocyte differentiation and foam cell formation in vitro by 7-ketocholesterol.
MedLine Citation:
PMID:  11792719     Owner:  NLM     Status:  MEDLINE    
Oxidized LDL (OxLDL) is composed of many potentially proatherogenic molecules, including oxysterols. Of the oxysterols, 7-ketocholesterol (7-KC) is found in relatively large abundance in OxLDL, as well as in atherosclerotic plaque and foam cells in vivo. Although there is evidence that 7-KC activates endothelial cells, its effect on monocytes is unknown. We tested the hypothesis that 7-KC may induce monocyte differentiation and promote foam cell formation. THP-1 cells were used as a monocyte model system and were treated with 7-KC over a range of concentrations from 0.5 to 10 microg/ml. Changes in cell adhesion properties, cell morphology, and expression of antigens characteristic of differentiated macrophages were monitored over a 7-day period. 7-KC promoted cells to firmly adhere and display morphologic features of differentiated macrophages; this effect was time and dose dependent and was markedly more potent than cholesterol treatment (45% of cells became adherent after 7 days of treatment with 7-KC at 10 microg/ml vs. less then 5% for control cells, P < 0.01). Similar effects were obtained when LDL enriched with 7-KC or OxLDL were added to THP-1 cells. 7-KC-differentiated cells expressed CD11b, CD36, and CD68, phagocytized latex beads, and formed lipid-laden foam cells after exposure to acetylated LDL or OxLDL. In contrast to 7-KC, oxysterols with known cell regulatory effects such as 25-hydroxycholesterol, 7beta-hydroxycholesterol, and (22R)-hydroxycholesterol did not effectively promote THP-1 differentiation. In conclusion, these results demonstrate for the first time that 7-KC, a prominent oxysterol formed in OxLDL by peroxidation of cholesterol, may play an important role in promoting monocyte differentiation and foam cell formation. These studies also suggest that 7-KC induces monocyte differentiation through a sterol-mediated regulatory pathway that remains to be characterized.
John M Hayden; Libuse Brachova; Karen Higgins; Lewis Obermiller; Alex Sevanian; Srikrishna Khandrika; Peter D Reaven
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.    
Journal Detail:
Title:  Journal of lipid research     Volume:  43     ISSN:  0022-2275     ISO Abbreviation:  J. Lipid Res.     Publication Date:  2002 Jan 
Date Detail:
Created Date:  2002-01-16     Completed Date:  2002-04-30     Revised Date:  2009-11-03    
Medline Journal Info:
Nlm Unique ID:  0376606     Medline TA:  J Lipid Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  26-35     Citation Subset:  IM    
Division of Endocrinology and Metabolism, Department of Medicine (CS/111E), Carl T. Hayden Veterans Affairs Medical Center, 650 E. Indian School Road, Phoenix, AZ 85012-1892, USA.
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MeSH Terms
Antigens, CD36
Cell Adhesion / drug effects
Cell Differentiation / drug effects*
Cell Line
Dose-Response Relationship, Drug
Foam Cells / cytology,  physiology*
Hydroxycholesterols / pharmacology
Ketocholesterols / metabolism,  pharmacology*
Lipoproteins, LDL / metabolism
Macrophages / cytology,  physiology*
Membrane Proteins*
Models, Biological
Monocytes / cytology,  drug effects*,  physiology
Protein Biosynthesis
RNA, Messenger / biosynthesis
Receptors, Immunologic / biosynthesis
Receptors, Lipoprotein*
Receptors, Scavenger
Scavenger Receptors, Class B
Reg. No./Substance:
0/Antigens, CD36; 0/Hydroxycholesterols; 0/Ketocholesterols; 0/Lipoproteins, LDL; 0/Membrane Proteins; 0/RNA, Messenger; 0/Receptors, Immunologic; 0/Receptors, Lipoprotein; 0/Receptors, Scavenger; 0/Scarb1 protein, mouse; 0/Scavenger Receptors, Class B; 0/oxidized low density lipoprotein; 2140-46-7/25-hydroxycholesterol; 566-28-9/7-ketocholesterol

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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