Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

0

Macrophage-specific inhibition of NF-κB activation impairs foam cell survival


ABSTRACT: Macrophage death in advanced atherosclerotic lesions is a key event in the conversion of benign lesions to vulnerable plaques. One fundamental transcription factor that has been shown to play a pivotal role in cell death/survival is nuclear factor kB (NF-kB). Still, the relevance of this key transcription factor for macrophage-derived foam cell survival has not been unequivocally resolved at the molecular level. THP-1 monocytic cell lines were generated in which NF-kB activation is specifically inhibited by overexpression of a trans-dominant, non-degradable form of IkBa (IkBa (32A/36A)) under control of the macrophage-specific SR-A promoter. A diminished lipid loading during NF-κB inhibition during foam cell formation was accompanied by increased cell death. A genome-wide expression profile of NF-kB-dependent genes during foam cell formation was established showing a widespread effect on the macrophage transcriptome. The three largest functional gene clusters identified and validated by independent techniques, were those involved in lipid metabolism, apoptosis and oxidative stress. The net result of these complex gene expression changes invoked by inhibition of NF-κB activation during lipid loading is a reduction of foam cell survival through caspase-dependent apoptosis. Thus, the NF-kB-dependent gene repertoire seems essential for sustained macrophage survival during the process of pathological lipid loading. Keywords: genetic modification, lipid loading, timecourse THP-1 cells and two different THP-1 IkB mutants (A3 and A12) were exposed to PMA to induce macrophage differentiation and subsequently loaded with oxidized LDL or vehicle for 5 or 8 days. One replicate per array, a total of 15 arrays. A common reference pool, composed of an equimolar mixture of all samples, was labeled with Cy3 and hybridized against the Cy5-labeled experimental sample.

ORGANISM(S): Homo sapiens

SUBMITTER: Anton Horrevoets 

PROVIDER: E-GEOD-12434 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

Similar Datasets

2009-08-11 | GSE12434 | GEO
2024-05-09 | PXD037534 | JPOST Repository
2012-12-31 | GSE8009 | GEO
| PRJNA113039 | ENA
2010-12-31 | GSE19926 | GEO
2018-10-17 | PXD001873 | Pride
2012-12-31 | GSE8334 | GEO
2012-12-31 | E-GEOD-8009 | biostudies-arrayexpress
2015-07-23 | E-GEOD-70126 | biostudies-arrayexpress
2010-12-31 | E-GEOD-19926 | biostudies-arrayexpress