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Novel candidate genes for atherosclerosis are identified by representational difference analysis-based transcript profiling of cholesterol-loaded macrophages

Andersson, T. (author)
Borang, S. (author)
Larsson, M. (author)
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Wirta, V. (author)
Wennborg, A. (author)
Karolinska Institutet
Lundeberg, Joakim (author)
KTH,Bioteknologi
Odeberg, Jacob (author)
Karolinska Institutet,KTH,Bioteknologi
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 (creator_code:org_t)
2002-09-20
2001
English.
In: Pathobiology (Basel). - : S. Karger AG. - 1015-2008 .- 1423-0291. ; 69:6, s. 304-314
  • Journal article (peer-reviewed)
Abstract Subject headings
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  • Objectives: To analyze the early gene expression in macrophages accompanying the phenotypic changes into foam cells upon exposure to oxidized low-density lipoprotein. To identify candidate genes and markers for further studies into the pathogenesis of atherosclerosis. Methods: Cells of the monocytic cell line THP-1 were activated by PMA and exposed to oxidized low-density lipoprotein. Gene expression profiles were investigated after 24 h, using a solid phase cDNA representational difference analysis (RDA) method and shotgun sequencing. Results were verified by microarray hybridization, and analyzed in the virtual chip display of a novel software tool for transcript profile exploration. Results: By comparing transcript profiles of exposed/unexposed cells, 1,984 transcript sequences, representing a total of 921 genes with altered expression levels in response to oxidized low-density lipoprotein exposure, were identified. Genes that are central to cell cycle control and proliferation, inflammatory response, and of pathways not previously implicated in atherosclerosis were identified. The data obtained is also made available on-line at http:// biobase.biotech.kth.se/thp1a for further exploration. Conclusion: The identification of new candidate genes for atherosclerotic disease through RDA-based transcript profiling facilitates further functional genomic studies in coronary artery disease. Candidate genetic polymorphism markers of potential clinical relevance can be identified by filtering information in genome variation databases through the virtual chip analysis of the transcript profiles and subsequently tested in association studies.

Keyword

gene expression
subtraction
virtual chip
atherosclerosis
representational difference analysis
oxidized low-density lipoprotein
THP-1
foam cell
macrophage
transcript profiling
wilms-tumor gene
low-density-lipoprotein
nitric-oxide synthase
ppar-gamma
cell-line
expression
differentiation
wt1
protein
thp-1

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ref (subject category)
art (subject category)

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