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Hypoxia converts hu...
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Boström, Pontus,1982Gothenburg University,Göteborgs universitet,Wallenberglaboratoriet,Wallenberg Laboratory
(author)
Hypoxia converts human macrophages into triglyceride-loaded foam cells.
- Article/chapterEnglish2006
Publisher, publication year, extent ...
Numbers
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LIBRIS-ID:oai:gup.ub.gu.se/119550
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https://gup.ub.gu.se/publication/119550URI
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https://doi.org/10.1161/01.ATV.0000229665.78997.0bDOI
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Subject category:ref swepub-contenttype
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Subject category:art swepub-publicationtype
Notes
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OBJECTIVE: Atherosclerotic lesions have regions that are hypoxic. Because the lesion contains macrophages that are loaded with lipid, we investigated whether hypoxia can influence the accumulation of lipids in these cells. METHODS AND RESULTS: Exposure of human macrophages to hypoxia for 24 hours resulted in an increased formation of cytosolic lipid droplets and an increased accumulation of triglycerides. Exposure of the macrophages to oxidized low-density lipoprotein (oxLDL) increased the accumulation of cytosolic lipid droplets because of an increase in cellular cholesterol esters. The accumulation of lipid droplets in oxLDL-treated cells was further increased after hypoxia, caused by an increased level of triglycerides. Expression analyses combined with immunoblot or RT-PCR demonstrated that hypoxia increased the expression of several genes that could promote the accumulation of lipid droplets. Hypoxia increased the mRNA and protein levels of adipocyte differentiation-related protein (ADRP). It is well known that an increased expression of ADRP increases the formation of lipid droplets. Hypoxia decreased the expression of enzymes involved in beta-oxidation (acyl-coenzyme A synthetase and acyl-coenzyme A dehydrogenase) and increased the expression of stearoyl-coenzyme A desaturase, an important enzyme in the fatty acid biosynthesis. Moreover, exposure to hypoxia decreased the rate of beta-oxidation, whereas the accumulation of triglycerides increased. CONCLUSIONS: The results demonstrate that exposure of human macrophages to hypoxia causes an accumulation of triglyceride-containing cytosolic lipid droplets. This indicates that the hypoxia present in atherosclerotic lesions can contribute to the formation of the lipid-loaded macrophages that characterize the lesion and to the accumulation of triglycerides in such lesions.
Subject headings and genre
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Acyl-CoA Dehydrogenase
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antagonists & inhibitors
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Anoxia
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metabolism
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pathology
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Cells
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Cultured
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Coenzyme A Ligases
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antagonists & inhibitors
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Cytosol
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metabolism
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Foam Cells
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metabolism
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pathology
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Humans
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Immunoblotting
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Lipid Metabolism
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drug effects
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Lipoproteins
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LDL
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pharmacology
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Macrophages
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metabolism
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pathology
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Membrane Proteins
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genetics
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metabolism
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RNA
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Messenger
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metabolism
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Reverse Transcriptase Polymerase Chain Reaction
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Stearoyl-CoA Desaturase
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metabolism
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Time Factors
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Triglycerides
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metabolism
Added entries (persons, corporate bodies, meetings, titles ...)
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Magnusson, Björn,1976Gothenburg University,Göteborgs universitet,Wallenberglaboratoriet,Wallenberg Laboratory(Swepub:gu)xmagnb
(author)
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Svensson, Per-Arne,1969Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Institute of Medicine, Department of Molecular and Clinical Medicine(Swepub:gu)xsvper
(author)
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Wiklund, Olov,1943Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Institute of Medicine, Department of Molecular and Clinical Medicine(Swepub:gu)xwikol
(author)
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Borén, Jan,1963Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Institute of Medicine, Department of Molecular and Clinical Medicine(Swepub:gu)xborej
(author)
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Carlsson, Lena M S,1957Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Institute of Medicine, Department of Molecular and Clinical Medicine(Swepub:gu)xcarle
(author)
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Ståhlman, Marcus,1975Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Institute of Medicine, Department of Molecular and Clinical Medicine(Swepub:gu)xstahm
(author)
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Olofsson, Sven-Olof,1947Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Institute of Medicine, Department of Molecular and Clinical Medicine(Swepub:gu)xolosv
(author)
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Mattsson Hultén, Lillemor,1951Gothenburg University,Göteborgs universitet,Wallenberglaboratoriet,Wallenberg Laboratory(Swepub:gu)xmatli
(author)
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Göteborgs universitetWallenberglaboratoriet
(creator_code:org_t)
Related titles
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In:Arteriosclerosis, thrombosis, and vascular biology26:8, s. 1871-61524-4636
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