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

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: Nov 13, 2014
• Journal: Arteriosclerosis thrombosis and vascular biology
• Print ISSN: 1079-5642
• 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
• Contract Date: Nov 13, 2014