Veronica A. Carroll
Antiangiogenic activity of a domain deletion mutant of tissue plasminogen activator containing kringle 2
Carroll, Veronica A.; Nikitenko, Leonid L.; Bicknell, Roy; Harris, Adrian L.
Authors
Dr Leonid Nikitenko L.Nikitenko@hull.ac.uk
Lecturer in Biomedical Sciences
Roy Bicknell
Adrian L. Harris
Abstract
Objective - The thrombolytic therapy drug, Reteplase, is a domain deletion mutant of tissue plasminogen activator (tPA), comprising the kringle 2 and protease (K2P) domains. Some kringle domains of hemostatic proteins are antiangiogenic and promote apoptosis. The objective of this study was to investigate whether K2P is an angiogenesis inhibitor because of the presence of kringle 2.
Methods and Results - K2P inhibited basic fibroblast growth factor-induced human endothelial cell proliferation and migration. Inhibition was not dependent on the protease activity of K2P because similar results were obtained with catalytically inactivated K2P, Purification of the kringle 2 domain derived from elastase cleavage of K2P at the Arg275-Ile 276 bond revealed that inhibition was mediated by this domain. In addition, K2P inhibited angiogenesis in vivo and increased endothelial cell apoptosis.
Conclusions - Wound healing and angiogenesis are severely compromised by K2P. These data provide new mechanistic insights into the bleeding complications observed in some patients while undergoing thrombolytic therapy with this drug. In addition, we identify the kringle 2 domain of tPA as a novel target for antiangiogenic therapy. © 2005 American Heart Association, Inc.
Citation
Carroll, V. A., Nikitenko, L. L., Bicknell, R., & Harris, A. L. (2005). Antiangiogenic activity of a domain deletion mutant of tissue plasminogen activator containing kringle 2. Arteriosclerosis, Thrombosis, and Vascular Biology, 25(4), 736-741. https://doi.org/10.1161/01.ATV.0000157980.15710.2b
Journal Article Type | Article |
---|---|
Publication Date | Feb 3, 2005 |
Deposit Date | May 3, 2022 |
Journal | Arteriosclerosis, Thrombosis, and Vascular Biology |
Print ISSN | 1079-5642 |
Publisher | American Heart Association |
Peer Reviewed | Peer Reviewed |
Volume | 25 |
Issue | 4 |
Pages | 736-741 |
DOI | https://doi.org/10.1161/01.ATV.0000157980.15710.2b |
Public URL | https://hull-repository.worktribe.com/output/3571068 |
You might also like
Quantitative proteomics reveals CLR interactome in primary human cells
(2024)
Journal Article
Abstract A020: Calcitonin receptor-like receptor is expressed in blood vessels in clear cell renal cell carcinoma and upregulated in endothelial cells co-cultured with tumor cells
(2023)
Presentation / Conference Contribution
Abstract B001: Calcitonin receptor-like receptor agonists induce p44/42 MAPK phosphorylation in VEGF-A-stimulated human blood endothelial cells after bevacizumab treatment
(2023)
Presentation / Conference Contribution