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dc.contributor.authorKramer, Carolyn D.
dc.contributor.authorWeinberg, Ellen O.
dc.contributor.authorGower, Adam C.
dc.contributor.authorHe, Xianbao
dc.contributor.authorMekasha, Samrawit
dc.contributor.authorSlocum, Connie
dc.contributor.authorBeaulieu, Lea M.
dc.contributor.authorWetzler, Lee
dc.contributor.authorAlekseyev, Yuriy
dc.contributor.authorGibson, Frank C. III
dc.contributor.authorFreedman, Jane E.
dc.contributor.authorIngalls, Robin R.
dc.contributor.authorGenco, Caroline A.
dc.date2022-08-11T08:09:43.000
dc.date.accessioned2022-08-23T16:40:52Z
dc.date.available2022-08-23T16:40:52Z
dc.date.issued2014-12-24
dc.date.submitted2015-09-04
dc.identifier.citationBMC Genomics. 2014 Dec 24;15:1176. doi: 10.1186/1471-2164-15-1176. <a href="http://dx.doi.org/10.1186/1471-2164-15-1176">Link to article on publisher's site</a>
dc.identifier.issn1471-2164 (Linking)
dc.identifier.doi10.1186/1471-2164-15-1176
dc.identifier.pmid25540039
dc.identifier.urihttp://hdl.handle.net/20.500.14038/39768
dc.description.abstractBACKGROUND: Atherosclerosis is a progressive disease characterized by inflammation and accumulation of lipids in vascular tissue. Porphyromonas gingivalis (Pg) and Chlamydia pneumoniae (Cp) are associated with inflammatory atherosclerosis in humans. Similar to endogenous mediators arising from excessive dietary lipids, these Gram-negative pathogens are pro-atherogenic in animal models, although the specific inflammatory/atherogenic pathways induced by these stimuli are not well defined. In this study, we identified gene expression profiles that characterize P. gingivalis, C. pneumoniae, and Western diet (WD) at acute and chronic time points in aortas of Apolipoprotein E (ApoE-/-) mice. RESULTS: At the chronic time point, we observed that P. gingivalis was associated with a high number of unique differentially expressed genes compared to C. pneumoniae or WD. For the top 500 differentially expressed genes unique to each group, we observed a high percentage (76%) that exhibited decreased expression in P. gingivalis-treated mice in contrast to a high percentage (96%) that exhibited increased expression in WD mice. C. pneumoniae treatment resulted in approximately equal numbers of genes that exhibited increased and decreased expression. Gene Set Enrichment Analysis (GSEA) revealed distinct stimuli-associated phenotypes, including decreased expression of mitochondrion, glucose metabolism, and PPAR pathways in response to P. gingivalis but increased expression of mitochondrion, lipid metabolism, carbohydrate and amino acid metabolism, and PPAR pathways in response to C. pneumoniae; WD was associated with increased expression of immune and inflammatory pathways. DAVID analysis of gene clusters identified by two-way ANOVA at acute and chronic time points revealed a set of core genes that exhibited altered expression during the natural progression of atherosclerosis in ApoE-/- mice; these changes were enhanced in P. gingivalis-treated mice but attenuated in C. pneumoniae-treated mice. Notable differences in the expression of genes associated with unstable plaques were also observed among the three pro-atherogenic stimuli. CONCLUSIONS: Despite the common outcome of P. gingivalis, C. pneumoniae, and WD on the induction of vascular inflammation and atherosclerosis, distinct gene signatures and pathways unique to each pro-atherogenic stimulus were identified. Our results suggest that pathogen exposure results in dysregulated cellular responses that may impact plaque progression and regression pathways.
dc.language.isoen_US
dc.relation<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=25540039&dopt=Abstract">Link to Article in PubMed</a>
dc.rights<p>© 2015 Kramer et al.; licensee BioMed Central. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (<a href="http://creativecommons.org/licenses/by/4.0">http://creativecommons.org/licenses/by/4.0</a>), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.</p>
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectAnimals
dc.subjectAorta
dc.subjectApolipoproteins E
dc.subjectChlamydophila pneumoniae
dc.subjectDiet, Western
dc.subject*Gene Expression Profiling
dc.subjectKinetics
dc.subjectMale
dc.subjectMice
dc.subjectMice, Inbred C57BL
dc.subjectMultigene Family
dc.subjectPlaque, Atherosclerotic
dc.subjectPorphyromonas gingivalis
dc.subjectCardiology
dc.subjectCardiovascular Diseases
dc.subjectGenomics
dc.subjectPathogenic Microbiology
dc.titleDistinct gene signatures in aortic tissue from ApoE-/- mice exposed to pathogens or Western diet
dc.typeJournal Article
dc.source.journaltitleBMC genomics
dc.source.volume15
dc.identifier.legacyfulltexthttps://escholarship.umassmed.edu/cgi/viewcontent.cgi?article=3570&amp;context=oapubs&amp;unstamped=1
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/oapubs/2566
dc.identifier.contextkey7559982
refterms.dateFOA2022-08-23T16:40:52Z
html.description.abstract<p>BACKGROUND: Atherosclerosis is a progressive disease characterized by inflammation and accumulation of lipids in vascular tissue. Porphyromonas gingivalis (Pg) and Chlamydia pneumoniae (Cp) are associated with inflammatory atherosclerosis in humans. Similar to endogenous mediators arising from excessive dietary lipids, these Gram-negative pathogens are pro-atherogenic in animal models, although the specific inflammatory/atherogenic pathways induced by these stimuli are not well defined. In this study, we identified gene expression profiles that characterize P. gingivalis, C. pneumoniae, and Western diet (WD) at acute and chronic time points in aortas of Apolipoprotein E (ApoE-/-) mice.</p> <p>RESULTS: At the chronic time point, we observed that P. gingivalis was associated with a high number of unique differentially expressed genes compared to C. pneumoniae or WD. For the top 500 differentially expressed genes unique to each group, we observed a high percentage (76%) that exhibited decreased expression in P. gingivalis-treated mice in contrast to a high percentage (96%) that exhibited increased expression in WD mice. C. pneumoniae treatment resulted in approximately equal numbers of genes that exhibited increased and decreased expression. Gene Set Enrichment Analysis (GSEA) revealed distinct stimuli-associated phenotypes, including decreased expression of mitochondrion, glucose metabolism, and PPAR pathways in response to P. gingivalis but increased expression of mitochondrion, lipid metabolism, carbohydrate and amino acid metabolism, and PPAR pathways in response to C. pneumoniae; WD was associated with increased expression of immune and inflammatory pathways. DAVID analysis of gene clusters identified by two-way ANOVA at acute and chronic time points revealed a set of core genes that exhibited altered expression during the natural progression of atherosclerosis in ApoE-/- mice; these changes were enhanced in P. gingivalis-treated mice but attenuated in C. pneumoniae-treated mice. Notable differences in the expression of genes associated with unstable plaques were also observed among the three pro-atherogenic stimuli.</p> <p>CONCLUSIONS: Despite the common outcome of P. gingivalis, C. pneumoniae, and WD on the induction of vascular inflammation and atherosclerosis, distinct gene signatures and pathways unique to each pro-atherogenic stimulus were identified. Our results suggest that pathogen exposure results in dysregulated cellular responses that may impact plaque progression and regression pathways.</p>
dc.identifier.submissionpathoapubs/2566
dc.contributor.departmentDepartment of Medicine, Division of Cardiovascular Medicine
dc.source.pages1176


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<p>© 2015 Kramer et al.; licensee BioMed Central. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (<a href="http://creativecommons.org/licenses/by/4.0">http://creativecommons.org/licenses/by/4.0</a>), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.</p>
Except where otherwise noted, this item's license is described as <p>© 2015 Kramer et al.; licensee BioMed Central. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (<a href="http://creativecommons.org/licenses/by/4.0">http://creativecommons.org/licenses/by/4.0</a>), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.</p>