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Induction of endothelial cell proliferation by recombinant and microparticle-tissue factor involves β1-integrin and extracellular signal regulated kinase activation

Collier, Mary E. W.; Ettelaie, Camille

Authors

Mary E. W. Collier



Abstract

Objective: Increased levels of circulating tissue factor (TF) in the form of microparticles increase the risk of thrombosis. However, any direct influence of microparticle-associated TF on vascular endothelial cell proliferation is not known. In this study, the influence of recombinant and microparticle- associated TF on endothelial cell proliferation and mitogen-activated protein kinase signaling mechanisms was examined. Methods and Results: Incubation of human coronary artery endothelial cells with lipidated recombinant full-length TF, or TF-containing microparticles (50 to 200 pmol/L TF), increased the rate of cell proliferation and induced phosphorylation of extracellular signal regulated kinase 1 in a TF-dependent manner. Inhibition of extracellular signal regulated kinase 1/2 using PD98059 or extracellular signal regulated kinase 1/2 antisense oligonucleotides or inhibition of c-Jun N-terminal kinase reduced recombinant TF-mediated cell proliferation. PD98059 also reduced cell proliferation in response to TF-containing microparticles. Inclusion of FVIIa (5 nmol/L) and FXa (10 nmol/L) or preincubation of cells with an inhibitory anti-FVIIa antibody had no additional influence on TF-mediated cell proliferation. However, preincubation of exogenous TF with a β1-integrin peptide (amino acids 579 to 799) reduced TF-mediated proliferation. Conclusion: High concentrations of recombinant or microparticle-associated TF stimulate endothelial cell proliferation through activation of the extracellular signal regulated kinase 1/2 pathway, mediated through a novel mechanism requiring the interaction of exogenous TF with cell surface β1-integrin and independent of FVIIa. © 2010 American Heart Association, Inc.

Citation

Collier, M. E. W., & Ettelaie, C. (2010). Induction of endothelial cell proliferation by recombinant and microparticle-tissue factor involves β1-integrin and extracellular signal regulated kinase activation. Arteriosclerosis, Thrombosis, and Vascular Biology, 30(9), 1810-1817. https://doi.org/10.1161/ATVBAHA.110.211854

Journal Article Type Article
Online Publication Date Jul 8, 2010
Publication Date Sep 1, 2010
Deposit Date Nov 13, 2014
Publicly Available Date Mar 28, 2024
Journal Arteriosclerosis thrombosis and vascular biology
Print ISSN 1079-5642
Electronic ISSN 1524-4636
Publisher American Heart Association
Peer Reviewed Peer Reviewed
Volume 30
Issue 9
Pages 1810-1817
DOI https://doi.org/10.1161/ATVBAHA.110.211854
Keywords Tissue factor; Microparticles; Extracellular signal regulated kinase 1/2; Endothelial cells; Beta 1-integrin
Public URL https://hull-repository.worktribe.com/output/462682
Publisher URL http://atvb.ahajournals.org/content/30/9/1810.abstract
Additional Information Author's accepted manuscript of article published in: Arteriosclerosis thrombosis and vascular biology, 2010, v.30, issue 9

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