title: β-Amyloid context intensifies vascular smooth muscle cells induced inflammatory response and de-differentiation.
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 Aβ1-40 -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 (VSMCs) toward an inflammatory/de-differentiated state. We found that Aβ1-40 -peptide alone neither induces an inflammatory response, nor decreases the expression of contractile markers; however, the inflammatory response of VSMCs exposed to Aβ1-40 -peptide prior to the addition of the pro-inflammatory cytokine IL-1β is greatly intensified compared with IL-1β-treated VSMCs previously un-exposed to Aβ1-40 -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 Aβ1-40 preactivation of the PI3 Kinase and possibly NFκB pathway; indeed, blocking the activation of these pathways during Aβ1-40 -peptide treatment completely suppressed the observed potentiation. Finally, strengthening the possible in vivo relevance of our findings, we evidenced that endothelial cells exposed to Aβ1-40 -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 VSMCs to an inflammatory/de-differentiated phenotype. Therefore, we suggest that acute inflammatory episodes may increase vascular alterations and contribute to the ontogenesis of CAA.
authors: UR4, Vieillissement, Stress et Inflammation, Université Paris 6, 7 quai St-Bernard, 75252, Paris cedex 5, France.
authors: Amélie
authors: A
authors: Vromman
authors: Nesrine
authors: N
authors: Trabelsi
authors: Clotilde
authors: C
authors: Rouxel
authors: Gilbert
authors: G
authors: Béréziat
authors: Isabelle
authors: I
authors: Limon
authors: Régis
authors: R
authors: Blaise
mesh_terms: D000544:Alzheimer Disease; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000098:blood supply*; D054337:Cell Dedifferentiation; D002478:Cells, Cultured; D016657:Cerebral Amyloid Angiopathy / Q000276:immunology; D017077:Culture Media, Conditioned; D004789:Enzyme Activation; D007249:Inflammation / Q000276:immunology*; D053583:Interleukin-1beta / Q000494:pharmacology; D051379:Mice; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D010446:Peptide Fragments / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D017077:Culture Media, Conditioned; D053583:Interleukin-1beta; D016328:NF-kappa B; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40); D019869:Phosphatidylinositol 3-Kinases