Heparanase and Platelet Factor-4 Induce Smooth Muscle Cell Proliferation and Migration via bFGF Release from the ECM

TitleHeparanase and Platelet Factor-4 Induce Smooth Muscle Cell Proliferation and Migration via bFGF Release from the ECM
Publication TypeJournal Article
Year of Publication2002
AuthorsMyler, HA, West, JL
JournalThe Journal of Biochemistry
Volume131
Issue6
Pagination913-922
Date Published04/2002
KeywordsBasic fibroblast growth factor; extracellular matrix; heparanase; PF4; restenosis
Abstract

Basic fibroblast growth factor (bFGF) has been shown to play an instrumental role in the cascade of events leading to restenosis; however, the mechanisms of bFGF activation following vascular injury have remained elusive. We have demonstrated that heparanase and platelet factor-4 (PF4), released from activated platelets at the site of injury, liberate bFGF from the extracellular matrix (ECM) of vascular smooth muscle cells (SMC), resulting in the induction of SMC proliferation with a bFGF-neutralozing antibody, suggesting that proliferation and migration. Increases responce to hiepararnase or PF4 are mediated by bFGF activation. When platelets were seeded on top of SMS proloferation and migration were inhibited by tratment with an anti-bFGF antibody. Furthermore, these increases in proloferation were completely inhibited by treatment with an anti-heoarananse antibody, suggesting that proliferation and migration in response to heparanase or PF4 are mediated by bFGF activation. When Platelets Platelet granulation products, such as heparanase and PF4, may liberate bFGF from extracellular sequestration, activating the growth factor and inducing the SMC proliferation and migration that contribute to the wound healing response following cascular injury.

Short TitleJ Biochem
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