Skip Navigation

Journal of Biochemistry 2006 139(3):339-345; doi:10.1093/jb/mvj061
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Request Permissions
Google Scholar
Right arrow Articles by Myler, H. A.
Right arrow Articles by West, J. L.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Myler, H. A.
Right arrow Articles by West, J. L.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© 2006 The Japanese Biochemical Society

Regular Paper

Novel Heparanase-Inhibiting Antibody Reduces Neointima Formation

Heather A. Myler1, Elizabeth A. Lipke2, Elizabeth E. Rice3 and Jennifer L. West3,*

1 Department of Biochemistry and Cell Biology, 2 Department of Chemical Engineering, and 3 Department of Bioengineering, Rice University, Houston, Texas 77005

* To whom correspondence should be addressed at: Department of Bioengineering, Rice University, 6100 Main St., P.O. Box 1892, MS-142, Houston, TX 77251, USA. Tel: +1-713-348-5955, Fax: +1-713-348-5877, E-mail: jwest{at}rice.edu

Basic fibroblast growth factor (bFGF), stored bound to heparan sulfate proteoglycans in the extracellular matrix (ECM) of the arterial media, may initiate smooth muscle cell (SMC) proliferation after coronary intervention, thus contributing to restenosis. bFGF mobilization from ECM stores after injury may be induced by platelet degranulation products such as heparanase. Therapies aimed at the inhibition of bFGF release and activation may assist in prevention of restenosis. To test this theory, we first examined the mobilization and activation of bFGF in the arterial media by platelet-derived heparanase. Heparanase, locally delivered to the rat carotid artery, was found to release bFGF and induce substantial SMC proliferation in the absence of actual vascular injury. An antibody that neutralizes heparanase was then developed and evaluated in a rat carotid balloon injury model. Local delivery of anti-heparanase IgG was found to inhibit bFGF release by approximately 60% ( p < 0·001) at 4 d; this correlated with the significant reduction in neointima formation observed at 14 d (intimal area/medial area: control 1·3 ± 0·3, anti-heparanase 0·35 ± 0·12, p < 0·0001). Platelet-derived heparanase is therefore likely to be important in initiating events leading to restenosis via bFGF mobilization. Furthermore, heparanase neutralization may assist in the prevention of restenosis following vascular injury.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 FASEB J.Home page
S. Gingis-Velitski, R. Ishai-Michaeli, I. Vlodavsky, and N. Ilan
Anti-heparanase monoclonal antibody enhances heparanase enzymatic activity and facilitates wound healing
FASEB J, December 1, 2007; 21(14): 3986 - 3993.
[Abstract] [Full Text] [PDF]


Disclaimer:
Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.