title: Epidermal growth factor prevents oligomeric amyloid-β induced angiogenesis deficits in vitro.
abstract: Cerebrovascular dysfunction is a critical component of Alzheimer's disease (AD) pathogenesis. Oligomeric amyloid-β42 (oAβ42) is considered a major contributor to AD progression. However, data are limited on the role of oAβ42 in brain endothelial cell vessel degeneration/angiogenesis, including the interaction with angiogenic mediators. Thus, the current study determined the effect of oAβ42 on angiogenesis in vitro, utilizing single brain endothelial cell cultures and triple cultures mimicking the microvascular unit (MVU: brain endothelial cells, astrocytes, and pericytes). oAβ42 dose-dependently reduced angiogenesis and induced vessel disruption. Critically, epidermal growth factor prevented oAβ42-induced deficits, implicating angiogenic pathways as potential therapeutics for AD.
authors.affiliation: Department of Anatomy and Cell Biology, University of Illinois at Chicago, Chicago, IL, USA.
authors.forename: Kevin P
authors.initials: KP
authors.lastname: Koster
authors.affiliation: Department of Anatomy and Cell Biology, University of Illinois at Chicago, Chicago, IL, USA.
authors.forename: Riya
authors.initials: R
authors.lastname: Thomas
authors.affiliation: Department of Anatomy and Cell Biology, University of Illinois at Chicago, Chicago, IL, USA.
authors.forename: Alan W J
authors.initials: AWJ
authors.lastname: Morris
authors.affiliation: Department of Anatomy and Cell Biology, University of Illinois at Chicago, Chicago, IL, USA leontai@uic.edu.
authors.forename: Leon M
authors.initials: LM
authors.lastname: Tai
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000378:metabolism / Q000633:toxicity*; D001253:Astrocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D018920:Coculture Techniques; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D006801:Humans; D055806:Microvessels / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008954:Models, Biological; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D010446:Peptide Fragments / Q000378:metabolism / Q000633:toxicity*; D020286:Pericytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D055503:Protein Multimerization
chemical_list: D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D004815:Epidermal Growth Factor
keywords: Alzheimer’s; angiogenesis; blood–brain barrier; cerebrovascular disease; endothelium; pericytes