Differential gene expression in multiple neurological, inflammatory and connective tissue pathways in a spontaneous model of human small vessel stroke.
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.
Affiliation: Centre for Clinical Brain Sciences, University of Edinburgh, Western General Hospital, Edinburgh; Department of Bioengineering, Imperial College London, London.Show MeSH
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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).
Affiliation: Centre for Clinical Brain Sciences, University of Edinburgh, Western General Hospital, Edinburgh; Department of Bioengineering, Imperial College London, London.