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Differential gene expression in multiple neurological, inflammatory and connective tissue pathways in a spontaneous model of human small vessel stroke.

Bailey EL, McBride MW, Beattie W, McClure JD, Graham D, Dominiczak AF, Sudlow CL, Smith C, Wardlaw JM - Neuropathol. Appl. Neurobiol. (2014)

Bottom Line: We found gene expression abnormalities, with fold changes ranging from 2.5 to 59 for the 10 most differentially expressed genes, related to endothelial tight junctions (reduced), nitric oxide bioavailability (reduced), myelination (impaired), glial and microglial activity (increased), matrix proteins (impaired), vascular reactivity (impaired) and albumin (reduced), consistent with protein expression defects in the same rats.All were present at age 5 weeks thus predating blood pressure elevation. 'Neurological' and 'inflammatory' pathways were more affected than 'vascular' functional pathways.Similar combined, individually modest, but multiple neurovascular unit defects, could explain susceptibility to spontaneous human SVD.

View Article: PubMed Central - PubMed

Affiliation: Centre for Clinical Brain Sciences, University of Edinburgh, Western General Hospital, Edinburgh; Department of Bioengineering, Imperial College London, London.

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Related in: MedlinePlus

A network from the ‘neurological disorders’ functional group, representing interactions between differentially expressed genes in SHRSP vs. WKY rats at 5 weeks of age, generated by Ingenuity Pathway Analysis software. Genes highlighted in red are down-regulated and in green are up-regulated in SHRSP compared with WKY. Solid lines indicate direct interactions. Dotted lines indicate indirect interactions. Details of affected genes are given in Tables S1 and S2.
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fig02: A network from the ‘neurological disorders’ functional group, representing interactions between differentially expressed genes in SHRSP vs. WKY rats at 5 weeks of age, generated by Ingenuity Pathway Analysis software. Genes highlighted in red are down-regulated and in green are up-regulated in SHRSP compared with WKY. Solid lines indicate direct interactions. Dotted lines indicate indirect interactions. Details of affected genes are given in Tables S1 and S2.

Mentions: Network analysis of the differential gene expression showed significant up-regulation in SHRSP of transcription factors (Figure 2) including Fos, JunB, Btg2 and early growth response genes (Egr1, Egr2, Egr4), genes central to cell signalling (Pgs2 [Cox2], Nfkbia, Pten, Sgk1), and C3; others were down-regulated (e.g. insulin-like growth factors [Igf2], albumin [Alb], Gfap and Mmp14).


Differential gene expression in multiple neurological, inflammatory and connective tissue pathways in a spontaneous model of human small vessel stroke.

Bailey EL, McBride MW, Beattie W, McClure JD, Graham D, Dominiczak AF, Sudlow CL, Smith C, Wardlaw JM - Neuropathol. Appl. Neurobiol. (2014)

A network from the ‘neurological disorders’ functional group, representing interactions between differentially expressed genes in SHRSP vs. WKY rats at 5 weeks of age, generated by Ingenuity Pathway Analysis software. Genes highlighted in red are down-regulated and in green are up-regulated in SHRSP compared with WKY. Solid lines indicate direct interactions. Dotted lines indicate indirect interactions. Details of affected genes are given in Tables S1 and S2.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4260148&req=5

fig02: A network from the ‘neurological disorders’ functional group, representing interactions between differentially expressed genes in SHRSP vs. WKY rats at 5 weeks of age, generated by Ingenuity Pathway Analysis software. Genes highlighted in red are down-regulated and in green are up-regulated in SHRSP compared with WKY. Solid lines indicate direct interactions. Dotted lines indicate indirect interactions. Details of affected genes are given in Tables S1 and S2.
Mentions: Network analysis of the differential gene expression showed significant up-regulation in SHRSP of transcription factors (Figure 2) including Fos, JunB, Btg2 and early growth response genes (Egr1, Egr2, Egr4), genes central to cell signalling (Pgs2 [Cox2], Nfkbia, Pten, Sgk1), and C3; others were down-regulated (e.g. insulin-like growth factors [Igf2], albumin [Alb], Gfap and Mmp14).

Bottom Line: We found gene expression abnormalities, with fold changes ranging from 2.5 to 59 for the 10 most differentially expressed genes, related to endothelial tight junctions (reduced), nitric oxide bioavailability (reduced), myelination (impaired), glial and microglial activity (increased), matrix proteins (impaired), vascular reactivity (impaired) and albumin (reduced), consistent with protein expression defects in the same rats.All were present at age 5 weeks thus predating blood pressure elevation. 'Neurological' and 'inflammatory' pathways were more affected than 'vascular' functional pathways.Similar combined, individually modest, but multiple neurovascular unit defects, could explain susceptibility to spontaneous human SVD.

View Article: PubMed Central - PubMed

Affiliation: Centre for Clinical Brain Sciences, University of Edinburgh, Western General Hospital, Edinburgh; Department of Bioengineering, Imperial College London, London.

Show MeSH
Related in: MedlinePlus