In:
Aging Cell, Wiley, Vol. 12, No. 3 ( 2013-06), p. 358-369
Abstract:
Several studies have shown that the accumulation of β‐amyloid peptides in the brain parenchyma or vessel wall generates an inflammatory environment. Some even suggest that there is a cause‐and‐effect relationship between inflammation and the development of Alzheimer's disease and/or cerebral amyloid angiopathy ( CAA ). Here, we studied the ability of wild‐type Aβ 1‐40 ‐peptide (the main amyloid peptide that accumulates in the vessel wall in sporadic forms of CAA ) to modulate the phenotypic transition of vascular smooth muscle cells ( VSMC s) toward an inflammatory/de‐differentiated state. We found that Aβ 1‐40 ‐peptide alone neither induces an inflammatory response, nor decreases the expression of contractile markers; however, the inflammatory response of VSMC s exposed to Aβ 1‐40 ‐peptide prior to the addition of the pro‐inflammatory cytokine IL ‐1β is greatly intensified compared with IL ‐1β‐treated VSMC s previously un‐exposed to Aβ 1‐40 ‐peptide. Similar conclusions could be drawn when tracking the decline of contractile markers. Furthermore, we found that the mechanism of this potentiation highly depends on an Aβ 1‐40 preactivation of the PI 3 Kinase and possibly NF κB pathway; indeed, blocking the activation of these pathways during Aβ 1‐40 ‐peptide treatment completely suppressed the observed potentiation. Finally, strengthening the possible in vivo relevance of our findings, we evidenced that endothelial cells exposed to Aβ 1‐40 ‐peptide generate an inflammatory context and have similar effects than the ones described with IL ‐1β. These results reinforce the idea that intraparietal amyloid deposits triggering adhesion molecules in endothelial cells, contribute to the transition of VSMC s to an inflammatory/de‐differentiated phenotype. Therefore, we suggest that acute inflammatory episodes may increase vascular alterations and contribute to the ontogenesis of CAA .
Type of Medium:
Online Resource
ISSN:
1474-9718
,
1474-9726
DOI:
10.1111/acel.2013.12.issue-3
Language:
English
Publisher:
Wiley
Publication Date:
2013
detail.hit.zdb_id:
2099130-7
SSG:
12
