Am J Physiol Cell Physiol AJP: Gastrointestinal and Liver Physiology
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
QUICK SEARCH:   [advanced]


     

Am J Physiol Cell Physiol (October 24, 2001). doi:10.1152/ajpcell.00339.2001
This Article
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
282/3/C578    most recent
00339.2001v1
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 Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Mason, J. C
Right arrow Articles by Haskard, D. O
Right arrow Search for Related Content
PubMed
Right arrow Articles by Mason, J. C
Right arrow Articles by Haskard, D. O

Articles in PresS, published online ahead of print October 24, 2001
Am J Physiol Cell Physiol, 10.1152/ajpcell.00339.2001
Submitted on July 24, 2001
Accepted on October 17, 2001

bFGF and VEGF act synergistically to enhance endothelial cytoprotection through upregulation of decay-accelerating factor

Justin C Mason1*, Elaine A Lidington1, Saifur R Ahmad1, and Dorian O Haskard1

1 Cardiovascular Medicine Unit, Imperial College School of Medicine, Hammersmith Hospital, London, United Kingdom

* To whom correspondence should be addressed. E-mail: justin.mason{at}ic.ac.uk.

The complement regulatory protein decay-accelerating factor (DAF) can be upregulated on endothelial cells (EC) by protein kinase C (PKC)-dependent and -independent pathways. We hypothesised that bFGF might induce EC DAF expression, providing a cytoprotective mechanism for angiogenic neovessels against complement-mediated injury. Incubation of umbilical vein, aortic and dermal EC with bFGF or VEGF significantly increased DAF expression. Growth factor-induced EC proliferation was inhibited by PKC antagonists. In contrast, although PKC antagonists inhibited VEGF-induced DAF expression, bFGF-induced DAF was unaffected. Investigation of MAPK pathways also revealed differences, with bFGF-induced DAF dependent upon p44/42 and p38 MAPK, while VEGF required activation of p38 MAPK alone. Upregulation of DAF by bFGF was functionally relevant, reducing C3 deposition on EC following complement activation by 60%, resulting in marked reduction in complement-mediated EC lysis. bFGF and VEGF were synergistic in terms of DAF expression resulting in enhanced cytoprotection. These observations reveal parallel PKC-dependent and independent pathways regulating complement activation during angiogenesis. Further elucidation of these may provide important insights into innate cytoprotective mechanisms in endothelium.




This article has been cited by other articles:


Home page
 Am. J. Pathol.Home page
P. Lundh von Leithner, J. H. Kam, J. Bainbridge, I. Catchpole, G. Gough, P. Coffey, and G. Jeffery
Complement Factor H Is Critical in the Maintenance of Retinal Perfusion
Am. J. Pathol., July 1, 2009; 175(1): 412 - 421.
[Abstract] [Full Text] [PDF]

Home page
 FASEB J.Home page
A. C. S. Sobke, D. Selimovic, V. Orlova, M. Hassan, T. Chavakis, A. N. Athanasopoulos, U. Schubert, M. Hussain, G. Thiel, K. T. Preissner, et al.
The extracellular adherence protein from Staphylococcus aureus abrogates angiogenic responses of endothelial cells by blocking Ras activation
FASEB J, December 1, 2006; 20(14): 2621 - 2623.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Gastrointest. Liver Physiol.Home page
T. Khomenko, S. Szabo, X. Deng, M. R. Jadus, H. Ishikawa, K. Osapay, Z. Sandor, and L. Chen
Suppression of early growth response factor-1 with egr-1 antisense oligodeoxynucleotide aggravates experimental duodenal ulcers
Am J Physiol Gastrointest Liver Physiol, June 1, 2006; 290(6): G1211 - G1218.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Cell Physiol.Home page
E. A. Lidington, R. Steinberg, A. R. Kinderlerer, R. C. Landis, M. Ohba, A. Samarel, D. O. Haskard, and J. C. Mason
A role for proteinase-activated receptor 2 and PKC-{epsilon} in thrombin-mediated induction of decay-accelerating factor on human endothelial cells
Am J Physiol Cell Physiol, December 1, 2005; 289(6): C1437 - C1447.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
B. C. Kuenen, G. Giaccone, R. Ruijter, A. Kok, C. Schalkwijk, K. Hoekman, and H. M. Pinedo
Dose-Finding Study of the Multitargeted Tyrosine Kinase Inhibitor SU6668 in Patients with Advanced Malignancies
Clin. Cancer Res., September 1, 2005; 11(17): 6240 - 6246.
[Abstract] [Full Text] [PDF]

Home page
 J. Am. Soc. Nephrol.Home page
A. Shimizu, Y. Masuda, T. Mori, H. Kitamura, M. Ishizaki, Y. Sugisaki, and Y. Fukuda
Vascular Endothelial Growth Factor165 Resolves Glomerular Inflammation and Accelerates Glomerular Capillary Repair in Rat Anti-Glomerular Basement Membrane Glomerulonephritis
J. Am. Soc. Nephrol., October 1, 2004; 15(10): 2655 - 2665.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
J. C. Mason, R. Steinberg, E. A. Lidington, A. R. Kinderlerer, M. Ohba, and D. O. Haskard
Decay-accelerating Factor Induction on Vascular Endothelium by Vascular Endothelial Growth Factor (VEGF) Is Mediated via a VEGF Receptor-2 (VEGF-R2)- and Protein Kinase C-{alpha}/{epsilon} (PKC{alpha}/{epsilon})-dependent Cytoprotective Signaling Pathway and Is Inhibited by Cyclosporin A
J. Biol. Chem., October 1, 2004; 279(40): 41611 - 41618.
[Abstract] [Full Text] [PDF]

Home page
 Arterioscler. Thromb. Vasc. Bio.Home page
R. Khurana, S. Shafi, J. Martin, and I. Zachary
Vascular Endothelial Growth Factor Gene Transfer Inhibits Neointimal Macrophage Accumulation in Hypercholesterolemic Rabbits
Arterioscler Thromb Vasc Biol, June 1, 2004; 24(6): 1074 - 1080.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
Visit Other APS Journals Online
Copyright © 1976 by the American Physiological Society.