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Am J Physiol Cell Physiol 282: C578-C587, 2002. First published October 24, 2001; doi:10.1152/ajpcell.00339.2001
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Vol. 282, Issue 3, C578-C587, March 2002

bFGF and VEGF synergistically enhance endothelial cytoprotection via decay-accelerating factor induction

Justin C. Mason, Elaine A. Lidington, Saifur R. Ahmad, and Dorian O. Haskard

British Heart Foundation Cardiovascular Medicine Unit, National Heart and Lung Institute, Imperial College School of Science, Technology and Medicine, Hammersmith Hospital, London W12 ONN, United Kingdom

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 hypothesized that basic fibroblast growth factor (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 vascular endothelial growth factor (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 mitogen-activated kinase (MAPK) pathways also revealed differences, with bFGF-induced DAF dependent on p44/42 and p38 MAPK and VEGF requiring activation of p38 MAPK alone. Upregulation of DAF by bFGF was functionally relevant, reducing C3 deposition on EC after complement activation by 60% and 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 pathways may provide important insights into innate cytoprotective mechanisms in endothelium.

complement; complement-mediated injury; angiogenesis


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