Aggregated LDL and lipid dispersions induce lysosomal cholesteryl ester accumulation in macrophage foam cells - PubMed (original) (raw)
. 2005 Oct;46(10):2052-60.
doi: 10.1194/jlr.M500059-JLR200. Epub 2005 Jul 16.
Affiliations
- PMID: 16024919
- DOI: 10.1194/jlr.M500059-JLR200
Free article
Aggregated LDL and lipid dispersions induce lysosomal cholesteryl ester accumulation in macrophage foam cells
Evelyn E Griffin et al. J Lipid Res. 2005 Oct.
Free article
Abstract
Macrophage foam cells in atherosclerotic lesions accumulate substantial cholesterol stores within large, swollen lysosomes. Previous studies with mildly oxidized low density lipoprotein (OxLDL)-treated THP-1 macrophages suggest an initial buildup of free cholesterol (FC), followed by an inhibition of lysosomal cholesteryl ester (CE) hydrolysis and a subsequent lysosomal accumulation of unhydrolyzed lipoprotein CE. We examined whether other potential sources of cholesterol found within atherosclerotic lesions could also induce similar lysosomal accumulation. Biochemical analysis combined with microscopic analysis showed that treatment of THP-1 macrophages with aggregated low density lipoprotein (AggLDL) or CE-rich lipid dispersions (DISP) produced a similar lysosomal accumulation of both FC and CE. Co-treatment with an ACAT inhibitor, CP113,818, confirmed that the CE accumulation was primarily the result of the inhibition of lysosomal CE hydrolysis. The rate of unhydrolyzed CE buildup was more rapid with DISP than with AggLDL. However, with both treatments, FC appeared to accumulate in lysosomes before the inhibition in hydrolysis and CE accumulation, a sequence shared with mildly OxLDL. Thus, lysosomal accumulation of FC and CE can be attributable to more general mechanisms than just the inhibition of hydrolysis by oxidized lipids.
Similar articles
- Lysosomal cholesterol accumulation inhibits subsequent hydrolysis of lipoprotein cholesteryl ester.
Jerome WG, Cox BE, Griffin EE, Ullery JC. Jerome WG, et al. Microsc Microanal. 2008 Apr;14(2):138-49. doi: 10.1017/S1431927608080069. Epub 2008 Mar 3. Microsc Microanal. 2008. PMID: 18312718 Free PMC article. - Lysosomal cholesterol derived from mildly oxidized low density lipoprotein is resistant to efflux.
Yancey PG, Jerome WG. Yancey PG, et al. J Lipid Res. 2001 Mar;42(3):317-27. J Lipid Res. 2001. PMID: 11254742 - Cholesterol and oxysterol metabolism and subcellular distribution in macrophage foam cells. Accumulation of oxidized esters in lysosomes.
Brown AJ, Mander EL, Gelissen IC, Kritharides L, Dean RT, Jessup W. Brown AJ, et al. J Lipid Res. 2000 Feb;41(2):226-37. J Lipid Res. 2000. PMID: 10681406 - The role of microscopy in understanding atherosclerotic lysosomal lipid metabolism.
Jerome WG, Yancey PG. Jerome WG, et al. Microsc Microanal. 2003 Feb;9(1):54-67. doi: 10.1017/S1431927603030010. Microsc Microanal. 2003. PMID: 12597787 Review. - Regulation of lipid droplet cholesterol efflux from macrophage foam cells.
Ouimet M, Marcel YL. Ouimet M, et al. Arterioscler Thromb Vasc Biol. 2012 Mar;32(3):575-81. doi: 10.1161/ATVBAHA.111.240705. Epub 2011 Dec 29. Arterioscler Thromb Vasc Biol. 2012. PMID: 22207731 Review.
Cited by
- Regulation of lipid stores and metabolism by lipophagy.
Liu K, Czaja MJ. Liu K, et al. Cell Death Differ. 2013 Jan;20(1):3-11. doi: 10.1038/cdd.2012.63. Epub 2012 May 18. Cell Death Differ. 2013. PMID: 22595754 Free PMC article. Review. - Selective regulation of macrophage lipid metabolism via nanomaterials' surface chemistry.
Wu J, Bai X, Yan L, Baimanov D, Cong Y, Quan P, Cai R, Guan Y, Bu W, Lin B, Wang J, Yu S, Li S, Chong Y, Li Y, Hu G, Zhao Y, Chen C, Wang L. Wu J, et al. Nat Commun. 2024 Sep 27;15(1):8349. doi: 10.1038/s41467-024-52609-7. Nat Commun. 2024. PMID: 39333092 Free PMC article. - Lysosomal cholesterol accumulation inhibits subsequent hydrolysis of lipoprotein cholesteryl ester.
Jerome WG, Cox BE, Griffin EE, Ullery JC. Jerome WG, et al. Microsc Microanal. 2008 Apr;14(2):138-49. doi: 10.1017/S1431927608080069. Epub 2008 Mar 3. Microsc Microanal. 2008. PMID: 18312718 Free PMC article. - Transcriptional analysis reveals that the intracellular lipid accumulation impairs gene expression profiles involved in insulin response-associated cardiac functionality.
Actis Dato V, Paz MC, Rey FE, Sánchez MC, Llorente-Cortés V, Chiabrando GA, Ceschin DG. Actis Dato V, et al. Sci Rep. 2023 May 30;13(1):8761. doi: 10.1038/s41598-023-35951-6. Sci Rep. 2023. PMID: 37253991 Free PMC article. - Lactobacillus attenuates progression of nonalcoholic fatty liver disease by lowering cholesterol and steatosis.
Lee NY, Shin MJ, Youn GS, Yoon SJ, Choi YR, Kim HS, Gupta H, Han SH, Kim BK, Lee DY, Park TS, Sung H, Kim BY, Suk KT. Lee NY, et al. Clin Mol Hepatol. 2021 Jan;27(1):110-124. doi: 10.3350/cmh.2020.0125. Epub 2020 Dec 3. Clin Mol Hepatol. 2021. PMID: 33317254 Free PMC article.