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Oxysterols present in atherosclerotic tissue decrease the expression of lipoprotein lipase messenger RNA in human monocyte-derived macrophages.

Artikel i vetenskaplig tidskrift
Författare Lillemor Mattsson Hultén
Helena Lindmark
U Diczfalusy
I Björkhem
Malin Ottosson
Y Liu
Göran Bondjers
Olov Wiklund
Publicerad i The Journal of clinical investigation
Volym 97
Nummer/häfte 2
Sidor 461-8
ISSN 0021-9738
Publiceringsår 1996
Publicerad vid Wallenberglaboratoriet
Institutionen för invärtesmedicin
Sidor 461-8
Språk en
Länkar dx.doi.org/10.1172/JCI118436
Ämnesord Animals, Arteriosclerosis, enzymology, pathology, Cells, Cultured, Cholesterol, metabolism, Down-Regulation, Foam Cells, enzymology, Gene Expression Regulation, Enzymologic, Humans, Hydroxycholesterols, metabolism, Lipoprotein Lipase, genetics, Macrophages, enzymology, Monocytes, cytology, RNA, Messenger, genetics, Rabbits
Ämneskategorier Cell- och molekylärbiologi

Sammanfattning

The presence of oxysterols in macrophages isolated from atherosclerotic tissue and the effect of oxysterols on the regulation of lipoprotein lipase (LPL) mRNA were studied. Both rabbit and human macrophages, freshly isolated from atherosclerotic aorta, show about the same distribution of oxysterols, analyzed by isotope dilution mass spectrometry, except that all three preparations of human arterial-derived macrophages contained high levels of 27-hydroxycholesterol, which was not found in rabbit macrophages. To determine if oxysterols regulate LPL expression, human monocyte-derived macrophages were incubated with different oxysterols. Incubation with 7 beta-hydroxycholesterol and 25-hydroxycholesterol resulted in a 70-75% reduction of LPL mRNA, analyzed by quantitative RT-PCR. Cholesterol and other tested oxysterols showed no effect on macrophage LPL mRNA expression compared with control. LPL activity in the medium was also reduced after exposure of the macrophages to 7 beta-hydroxycholesterol and 25-hydroxycholesterol. In conclusion, we have demonstrated accumulation of oxysterols in macrophage-derived foam cells isolated from atherosclerotic aorta. There was suppression of LPL mRNA in human monocyte-derived macrophages after incubation with 7 beta-hydroxycholesterol and 25-hydroxycholesterol. It is tempting to suggest that an exposure to oxysterols may explain our earlier observation of a low level of LPL mRNA in arterial foam cells.

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