If you are experiencing problems downloading PDF or HTML fulltext, our helpdesk recommend clearing your browser cache and trying again. If you need help in clearing your cache, please click here . Still need help? Email help@ingentaconnect.com

Free Content Pathogenic Aβ induces the expression and activation of matrix metalloproteinase-2 in human cerebrovascular smooth muscle cells

You have access to the full text article on a website external to ingentaconnect.

Please click here to view this article on Wiley Online Library.

You may be required to register and activate access on Wiley Online Library before you can obtain the full text. If you have any queries please visit Wiley Online Library

Download Article:

Abstract:

Abstract

Cerebral amyloid angiopathy (CAA) is a major pathological feature of Alzheimer's disease and related disorders. Human cerebrovascular smooth muscle (HCSM) cells, which are intimately associated with CAA, have been used as an in vitro model system to investigate pathologic interactions with amyloid β protein (Aβ). Previously we have shown that pathogenic forms of Aβ induce several pathologic responses in HCSM cells including fibril assembly at the cell surface, increase in the levels of Aβ precursor, and apoptotic cell death. Here we show that pathogenic Aβ stimulates the expression and activation of matrix metalloproteinase-2 (MMP-2). Furthermore, we demonstrate that the increase in MMP-2 activation is largely caused by increased expression of membrane type-1 (MT1)-MMP expression, the primary MMP-2 activator. Finally, treatment with MMP-2 inhibitors resulted in increased HCSM cell viability in the presence of pathogenic Aβ. Our findings suggest that increased expression and activation of MMP-2 may contribute to HCSM cell death in response to pathogenic Aβ. In addition, these activities may also contribute to loss of vessel wall integrity in CAA resulting in hemorrhagic stroke. Therefore, further understanding into the role of MMPs in HCSM cell degeneration may facilitate designing therapeutic strategies to treat CAA found in AD and related disorders.

Keywords: Alzheimer's disease; amyloid β protein; gelatinase; human cerebrovascular smooth muscle cells; matrix metalloproteinase; β-amyloid precursor protein

Document Type: Research Article

DOI: http://dx.doi.org/10.1046/j.1471-4159.2003.01745.x

Affiliations: Department of Medicine, Stony Brook University, Stony Brook, New York, USA

Publication date: June 1, 2003

Related content

Tools

Favourites

Share Content

Access Key

Free Content
Free content
New Content
New content
Open Access Content
Open access content
Subscribed Content
Subscribed content
Free Trial Content
Free trial content
Cookie Policy
X
Cookie Policy
ingentaconnect website makes use of cookies so as to keep track of data that you have filled in. I am Happy with this Find out more