Abstract：
:In late-stage atherosclerosis, much of the cholesterol in macrophage foam cells resides within enlarged lysosomes. Similarly, human macrophages incubated in vitro with modified LDLs contain significant amounts of lysosomal free cholesterol and cholesteryl ester (CE), which disrupts lysosomal function similar to macrophages in atherosclerotic lesions. The lysosomal cholesterol cannot be removed, even in the presence of strong efflux promoters. Thus, efflux of sterol is prevented. In the artery wall, foam cells interact with triglyceride-rich particles (TRPs) in addition to modified LDLs. Little is known about how TRP metabolism affects macrophage cholesterol. Therefore, we explored the effect of TRP on intracellular CE metabolism. Triglyceride (TG), delivered to lysosomes in TRP, reduced CE accumulation by 50%. Increased TG levels within the cell, particularly within lysosomes, correlated with reductions in CE content. The volume of cholesterol-engorged lysosomes decreased after TRP treatment, indicating cholesterol was cleared. Lysosomal TG also reduced the cholesterol-induced inhibition of lysosomal acidification allowing lysosomes to remain active. Enhanced degradation and clearance of CE may be explained by movement of cholesterol out of the lysosome to sites where it is effluxed. Thus, our results show that introduction of TG into CE-laden foam cells influences CE metabolism and, potentially, atherogenesis.-Ullery-Ricewick, J. C., B. E. Cox, E. E. Griffin, and W. G. Jerome. Triglyceride alters lysosomal cholesterol ester metabolism in cholesteryl ester-laden macrophage foam cells.
journal_name
J Lipid Resjournal_title
Journal of lipid researchauthors
Ullery-Ricewick JC,Cox BE,Griffin EE,Jerome WGdoi
10.1194/jlr.M800659-JLR200subject
Has Abstractpub_date
2009-10-01 00:00:00pages
2014-26issue
10eissn
0022-2275issn
1539-7262pii
M800659-JLR200journal_volume
50pub_type
杂志文章abstract：:Since the discovery of proprotein convertase subtilisin/kexin type 9 (PCSK9) as an attractive target in the treatment of hypercholesterolemia, multiple anti-PCSK9 therapeutic modalities have been pursued in drug development. The objective of this research is to set the stage for the quantitative benchmarking of two an...
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journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1980-03-01 00:00:00
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journal_title：Journal of lipid research
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doi：
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journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1986-11-01 00:00:00
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journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1980-09-01 00:00:00
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journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
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journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
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journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1966-11-01 00:00:00
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journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1992-03-01 00:00:00
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journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1988-05-01 00:00:00
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journal_title：Journal of lipid research
pub_type： 杂志文章
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journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1986-10-01 00:00:00
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pub_type： 杂志文章
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更新日期：2018-01-01 00:00:00
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journal_title：Journal of lipid research
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journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1975-03-01 00:00:00
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journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1969-07-01 00:00:00
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journal_title：Journal of lipid research
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更新日期：2014-11-01 00:00:00
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journal_title：Journal of lipid research
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doi：
更新日期：1991-04-01 00:00:00
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journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1990-10-01 00:00:00
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journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1995-04-01 00:00:00
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更新日期：2017-11-01 00:00:00
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journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1997-03-01 00:00:00
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