Phytosterols differentially influence ABC transporter expression, cholesterol efflux and inflammatory cytokine secretion in macrophage foam cells

Nadezhda S. Sabeva, Christopher M. McPhaul, Xiangan Li, Theodore Cory, David J. Feola, Gregory A. Graf

Research output: Contribution to journalArticle

41 Citations (Scopus)

Abstract

Phytosterol supplements lower low-density lipoprotein (LDL) cholesterol, but accumulate in vascular lesions of patients and limit the anti-atherosclerotic effects of LDL lowering in apolipoprotein E (Apo E)-deficient mice, suggesting that the cholesterol-lowering benefit of phytosterol supplementation may not be fully realized. Individual phytosterols have cell-type specific effects that may be either beneficial or deleterious with respect to atherosclerosis, but little is known concerning their effects on macrophage function. The effects of phytosterols on ABCA1 and ABCG1 abundance, cholesterol efflux and inflammatory cytokine secretion were determined in cultured macrophage foam cells. Among the commonly consumed phytosterols, stigmasterol increased expression of ABCA1 and ABCG1 and increased efflux of cholesterol to apolipoprotein (Apo) AI and high-density lipoprotein (HDL). Campesterol and sitosterol had no effect on ABCA1 or ABCG1 levels. Sitosterol had no effect on cholesterol efflux to Apo AI or HDL, whereas campesterol had a modest but significant reduction in cholesterol efflux to HDL in THP-1 macrophages. Whereas stigmasterol blunted aggregated LDL (agLDL) induced increases in tumor necrosis factor (TNF)-α, interleukin (IL)-6 and IL-1β secretion, sitosterol exacerbated these effects. The presence of campesterol had no effect on agLDL-induced inflammatory cytokine secretion from THP-1 macrophages. In conclusion, the presence of stigmasterol in modified lipoproteins promoted cholesterol efflux and suppressed inflammatory cytokine secretion in response to lipid loading in macrophage foam cells. While campesterol was largely inert, the presence of sitosterol increased the proinflammatory cytokine secretion.

Original languageEnglish (US)
Pages (from-to)777-783
Number of pages7
JournalJournal of Nutritional Biochemistry
Volume22
Issue number8
DOIs
StatePublished - Aug 1 2011

Fingerprint

Phytosterols
Foam Cells
ATP-Binding Cassette Transporters
Macrophages
Foams
Stigmasterol
Cholesterol
Cytokines
HDL Lipoproteins
Apolipoprotein A-I
LDL Lipoproteins
Apolipoproteins E
Interleukin-1
LDL Cholesterol
Blood Vessels
Interleukin-6
Atherosclerosis
Tumor Necrosis Factor-alpha
Lipoproteins
Lipids

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Clinical Biochemistry
  • Molecular Biology
  • Endocrinology, Diabetes and Metabolism
  • Nutrition and Dietetics

Cite this

Phytosterols differentially influence ABC transporter expression, cholesterol efflux and inflammatory cytokine secretion in macrophage foam cells. / Sabeva, Nadezhda S.; McPhaul, Christopher M.; Li, Xiangan; Cory, Theodore; Feola, David J.; Graf, Gregory A.

In: Journal of Nutritional Biochemistry, Vol. 22, No. 8, 01.08.2011, p. 777-783.

Research output: Contribution to journalArticle

Sabeva, Nadezhda S. ; McPhaul, Christopher M. ; Li, Xiangan ; Cory, Theodore ; Feola, David J. ; Graf, Gregory A. / Phytosterols differentially influence ABC transporter expression, cholesterol efflux and inflammatory cytokine secretion in macrophage foam cells. In: Journal of Nutritional Biochemistry. 2011 ; Vol. 22, No. 8. pp. 777-783.
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