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The β‐amyloid peptide of Alzheimer's disease decreases adhesion of vascular smooth muscle cells to the basement membrane
Author(s) -
Mok Su San,
Losic Dusan,
Barrow Colin J.,
Turner Bradley J.,
Masters Colin L.,
Martin Lisandra L.,
Small David H.
Publication year - 2006
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2005.03539.x
Subject(s) - perlecan , laminin , matrigel , basement membrane , microbiology and biotechnology , vascular smooth muscle , extracellular matrix , cell adhesion , chemistry , biology , proteoglycan , biochemistry , cell , endocrinology , smooth muscle
Cerebral amyloid angiopathy (CAA) is a major feature of Alzheimer's disease pathology. In CAA, degeneration of vascular smooth muscle cells (VSMCs) occurs close to regions of the basement membrane where the amyloid protein (Aβ) builds up. In this study, the possibility that Aβ disrupts adhesive interactions between VSMCs and the basement membrane was examined. VSMCs were cultured on a commercial basement membrane substrate (Matrigel). The presence of Aβ in the Matrigel decreased cell‐substrate adhesion and cell viability. Full‐length oligomeric Aβ was required for the effect, as N‐ and C‐terminally truncated peptide analogues did not inhibit adhesion. Aβ that was fluorescently labelled at the N‐terminus (fluo‐Aβ) bound to Matrigel as well as to the basement membrane heparan sulfate proteoglycan (HSPG) perlecan and laminin. Adhesion of VSMCs to perlecan or laminin was decreased by Aβ. As perlecan influences VSMC viability through the extracellular signal‐regulated kinase (ERK)1/2 signalling pathway, the effect of Aβ1–40 on ERK1/2 phosphorylation was examined. The level of phospho‐ERK1/2 was decreased in cells following Aβ treatment. An inhibitor of ERK1/2 phosphorylation enhanced the effect of Aβ on cell adhesion. The studies suggest that Aβ can decrease VSMC viability by disrupting VSMC–extracellular matrix (ECM) adhesion.