Phytosterols differentially influence ABC transporter expression, cholesterol efflux and inflammatory cytokine secretion in macrophage foam cells.
Nadezhda S. Sabeva,Christopher M. McPhaul,Xiang-An Li,Theodore J. Cory,David J. Feola,Gregory A. Graf +5 more
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The presence of stigmasterol in modified lipoproteins promoted cholesterol efflux and suppressed inflammatory cytokine secretion in response to lipid loading in macrophage foam cells, suggesting that the cholesterol-lowering benefit of phytosterol supplementation may not be fully realized.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.read more
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Plant sterols and plant stanols in the management of dyslipidaemia and prevention of cardiovascular disease
Helena Gylling,Jogchum Plat,Stephen D. Turley,Henry N. Ginsberg,Lars Ellegård,Wendy Jessup,Peter B. Jones,Dieter Lütjohann,Winfried Maerz,Winfried Maerz,Luis Masana,Günther Silbernagel,Bart Staels,Jan Borén,Alberico L. Catapano,Guy De Backer,John E. Deanfield,Olivier S. Descamps,Petri T. Kovanen,Gabriele Riccardi,Lale Tokgozoglu,M. John Chapman +21 more
TL;DR: Functional foods with plant sterols/stanols may be considered in individuals with high cholesterol levels at intermediate or low global cardiovascular risk who do not qualify for pharmacotherapy and as an adjunct to pharmacologic therapy in high and very high risk patients who fail to achieve LDL-C targets on statins or are statin- intolerant.
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Sterol intermediates from cholesterol biosynthetic pathway as liver X receptor ligands
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Network pharmacology-based prediction of active compounds and molecular targets in Yijin-Tang acting on hyperlipidaemia and atherosclerosis.
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