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: Across all ages, biological pathway analysis using IPA showed that the most significantly differentially expressed genes were in the acute phase response signalling pathway, but other pathways including circadian rhythm and complement were also affected (Figure 3). In the acute phase pathway, complement factor 3 (C3) was up-regulated, while Alb and transcription factor 4 were down-regulated. All three components of the complement pathway (classic, lectin and alternate) were affected (C3 up-regulated, C2 and C4 down-regulated) (Figure 4). The top five affected pathways also included genes associated with tight junction structure and signalling in 16- and 21-week-old SHRSP.
Affiliation: Centre for Clinical Brain Sciences, University of Edinburgh, Western General Hospital, Edinburgh; Department of Bioengineering, Imperial College London, London.