on December 14, 2006
Published online before print December 14, 2006, doi: 10.1161/01.ATV.0000255309.38699.6c
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Submitted on August 2, 2006
Accepted on November 23, 2006
Vascular Endothelial Growth Factor Synergistically Enhances Induction of E-Selectin by Tumor Necrosis Factor-
Anita K Stannard ;
From BHF Laboratories, Department of Medicine, University College London, United Kingdom.
* To whom correspondence should be addressed. E-mail: i.zachary{at}ucl.ac.uk.
Objective--The regulation of endothelial cell adhesion molecules (CAMs) by vascular endothelial growth factor (VEGF) was investigated in cell cultures and in a rabbit model of atherogenic neointima formation.
Methods and Results--VEGF regulation of vascular CAM-1 (vascular cell adhesion molecule, intercellular CAM-1 (intercellular adhesion molecule), and E-selectin were investigated in human umbilical vein endothelial cells using quantitative polymerase chain reaction, enzyme-linked immunosorbent assay, and flow cytometry, and in the rabbit collar model of atherogenic macrophage accumulation by immunostaining. VEGF alone caused no significant induction of vascular cell adhesion molecule-1, intercellular adhesion molecule-1, or E-selectin compared with tumor necrosis factor-
. In both hypercholesterolemic and normal rabbits, adenoviral VEGF-A165 expression caused no increase in endothelial vascular cell adhesion molecule-1 or E-selectin. In contrast, pretreatment of human umbilical vein endothelial cells with VEGF significantly increased E-selectin expression induced by tumor necrosis factor-, compared with tumor necrosis factor- alone, whereas vascular cell adhesion molecule-1 and intercellular adhesion molecule-1 were unaffected. VEGF similarly enhanced IL-1
-induced E-selectin upregulation. VEGF also synergistically increased tumor necrosis factor--induced E-selectin mRNA and shedding of soluble E-selectin. Synergistic upregulation of E-selectin expression by VEGF was mediated via VEGF receptor-2 and calcineurin signaling.
Conclusions--VEGF alone does not activate endothelium to induce CAM expression; instead, VEGF "primes" endothelial cells, sensitizing them to cytokines leading to heightened selective pro-inflammatory responses, including upregulation of E-selectin.
Key words: cell adhesion molecules • endothelial cells • IL-1
This article has been cited by other articles:
 |
|
 |
|
  V. V. Snegovskikh, F. Schatz, F. Arcuri, P. Toti, U. A. Kayisli, W. Murk, Guoyang Luo, C. J. Lockwood, and E. R. Norwitz Intra-Amniotic Infection Upregulates Decidual Cell Vascular Endothelial Growth Factor (VEGF) and Neuropilin-1 and -2 Expression: Implications for Infection-Related Preterm Birth Reproductive Sciences, August 1, 2009; 16(8): 767 - 780. [Abstract] [PDF]
|
|
|
|
 |
|
 T. E. Walshe, V. S. Dole, A. S.R. Maharaj, I. S. Patten, D. D. Wagner, and P. A. D'Amore Inhibition of VEGF or TGF-{beta} Signaling Activates Endothelium and Increases Leukocyte Rolling Arterioscler Thromb Vasc Biol, August 1, 2009; 29(8): 1185 - 1192. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Q. Hao, L. Wang, and H. Tang Vascular endothelial growth factor induces protein kinase D-dependent production of proinflammatory cytokines in endothelial cells Am J Physiol Cell Physiol, April 1, 2009; 296(4): C821 - C827. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Tabatabai, C. Herrmann, G. von Kurthy, M. Mittelbronn, S. Grau, B. Frank, R. Mohle, M. Weller, and W. Wick VEGF-dependent induction of CD62E on endothelial cells mediates glioma tropism of adult haematopoietic progenitor cells Brain, October 1, 2008; 131(10): 2579 - 2595. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Weishaupt, K. N. Munoz, E. Buzney, T. S. Kupper, and R. C. Fuhlbrigge T-Cell Distribution and Adhesion Receptor Expression in Metastatic Melanoma Clin. Cancer Res., May 1, 2007; 13(9): 2549 - 2556. [Abstract] [Full Text] [PDF]
|
|