dc.date.accessioned | 2013-03-12T08:49:22Z | |
dc.date.available | 2013-03-12T08:49:22Z | |
dc.date.issued | 2007 | en_US |
dc.date.submitted | 2007-12-02 | en_US |
dc.identifier.citation | Sandvik, Gunhild Kile. Spatial distribution of NF-kappaB transcriptional activity and expression of pro-inflammatory and cytoprotective proteins in murine aorta. Hovedoppgave, University of Oslo, 2007 | en_US |
dc.identifier.uri | http://hdl.handle.net/10852/12184 | |
dc.description.abstract | Vascular inflammation and atherosclerosis occur predominantly at branches and bends of arteries that are exposed to complex hemodynamics, whereas straight arteries exposed to unidirectional laminar flow are protected. Recent studies of murine arteries have revealed that complex hemodynamics are associated with enhanced endothelial expression of RelA, a member of the NF-ƒÛB family of transcription factors that regulates inflammation and apoptosis by inducing both pro-inflammatory (e.g. VCAM-1) and cytoprotective (e.g. A1) molecules. The distribution of NF-ƒÛB/RelA and the expression of NF-ƒÛB-dependent proteins in the murine aortic endothelium were evaluated by en face antibody staining of aortae followed by confocal microscopy and image analysis.
In C57BL/6 mice, RelA expression was significantly elevated in areas of complex hemodynamics. Also, after lipopolysaccharide treatment, the pro-inflammatory NF-ƒÛB dependent protein VCAM-1 and the cytoprotective protein A1 were increased in the endothelium of this area. Furthermore, transgenic luciferase reporter mice revealed that NF-ƒÛB transcriptional activity was strongly induced in areas of complex hemodynamics. This suggests that endothelial cells exposed to complex hemodynamics may be primed for enhanced NF-ƒÛB activation and induction of pro-inflammatory proteins on encountering activatory stimuli.
The protective effect of laminar flow on arteries may be a result of the activation of antioxidant genes via an Nrf2/EpRE-dependent transcriptional pathway. I examined this idea by assessing the expression levels of Nrf2 and its activity in regions of the murine aorta exposed to either complex or uniform hemodynamics. I observed by immunohistostaining that Nrf2 protein levels were increased in endothelial cells at the atherosusceptible region (exposed to complex flow) compared to the atheroresistant region (exposed to uniform flow). However, these data were not consistent with subsequent analyses of transgenic mice containing an Nrf2 (EpRE)-luciferase reporter which revealed that Nrf2 transcriptional activities were similar in atherosusceptible and atheroresistant regions. I conclude that although Nrf2 is expressed at elevated levels in atherosusceptible regions of the aorta its transcriptional activity is uniform throughout the aorta. These data do not support the hypothesis that enhanced Nrf2 activities are responsible for protecting arteries exposed to uniform hemodynamics from inflammation.
We conclude that the hemodynamic environment in arteries may have a pivotal role in the expansion and progression of atherosclerotic lesion. My data suggests that NF-ƒÛB may be an important determinant of the susceptibility of arteries to inflammation, whereas I did not find evidence for a role for Nrf2. Thus the NF-ƒÛB signal transduction pathway could serve as a novel and attractive therapeutic target for the prevention and treatment of atherosclerosis. | nor |
dc.language.iso | nob | en_US |
dc.subject | NF-kappaB aterosclerose hemodynamikk inflammasjon betennelse | en_US |
dc.title | Spatial distribution of NF-kappaB transcriptional activity and expression of pro-inflammatory and cytoprotective proteins in murine aorta | en_US |
dc.type | Master thesis | en_US |
dc.date.updated | 2008-02-26 | en_US |
dc.creator.author | Sandvik, Gunhild Kile | en_US |
dc.subject.nsi | VDP::568 | en_US |
dc.identifier.bibliographiccitation | info:ofi/fmt:kev:mtx:ctx&ctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:dissertation&rft.au=Sandvik, Gunhild Kile&rft.title=Spatial distribution of NF-kappaB transcriptional activity and expression of pro-inflammatory and cytoprotective proteins in murine aorta&rft.inst=University of Oslo&rft.date=2007&rft.degree=Hovedoppgave | en_US |
dc.identifier.urn | URN:NBN:no-18614 | en_US |
dc.type.document | Hovedoppgave | en_US |
dc.identifier.duo | 68450 | en_US |
dc.contributor.supervisor | Paul Evans, Harald Thidemann Johansen | en_US |
dc.identifier.bibsys | 080310745 | en_US |
dc.identifier.fulltext | Fulltext https://www.duo.uio.no/bitstream/handle/10852/12184/1/Thesis.pdf | |