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

John M. Hayden, Libuse Brachova, Karen Higgins, Lewis Obermiller, Alex Sevanian, Srikrishna Khandrika, Peter D. Reaven

Research output: Contribution to journalArticle

92 Citations (Scopus)

Abstract

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 μg/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 μg/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, 7β-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.

Original languageEnglish (US)
Pages (from-to)26-35
Number of pages10
JournalJournal of Lipid Research
Volume43
Issue number1
StatePublished - Feb 12 2002
Externally publishedYes

Fingerprint

Foam Cells
Foams
Monocytes
Macrophages
7-ketocholesterol
In Vitro Techniques
Cholesterol
Hydroxycholesterols
Cell adhesion
Endothelial cells
Latex
Sterols
Atherosclerotic Plaques
Microspheres
Cell Adhesion
LDL Cholesterol
oxidized low density lipoprotein
Endothelial Cells

Keywords

  • Oxidized LDL
  • Oxysterol
  • THP-1 cells

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology
  • Cell Biology

Cite this

Hayden, J. M., Brachova, L., Higgins, K., Obermiller, L., Sevanian, A., Khandrika, S., & Reaven, P. D. (2002). Induction of monocyte differentiation and foam cell formation in vitro by 7-ketocholesterol. Journal of Lipid Research, 43(1), 26-35.

Induction of monocyte differentiation and foam cell formation in vitro by 7-ketocholesterol. / Hayden, John M.; Brachova, Libuse; Higgins, Karen; Obermiller, Lewis; Sevanian, Alex; Khandrika, Srikrishna; Reaven, Peter D.

In: Journal of Lipid Research, Vol. 43, No. 1, 12.02.2002, p. 26-35.

Research output: Contribution to journalArticle

Hayden, JM, Brachova, L, Higgins, K, Obermiller, L, Sevanian, A, Khandrika, S & Reaven, PD 2002, 'Induction of monocyte differentiation and foam cell formation in vitro by 7-ketocholesterol', Journal of Lipid Research, vol. 43, no. 1, pp. 26-35.
Hayden JM, Brachova L, Higgins K, Obermiller L, Sevanian A, Khandrika S et al. Induction of monocyte differentiation and foam cell formation in vitro by 7-ketocholesterol. Journal of Lipid Research. 2002 Feb 12;43(1):26-35.
Hayden, John M. ; Brachova, Libuse ; Higgins, Karen ; Obermiller, Lewis ; Sevanian, Alex ; Khandrika, Srikrishna ; Reaven, Peter D. / Induction of monocyte differentiation and foam cell formation in vitro by 7-ketocholesterol. In: Journal of Lipid Research. 2002 ; Vol. 43, No. 1. pp. 26-35.
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