This Article Full Text Full Text (PDF) Data Supplement All Versions of this Article: 27/3/494    most recent 01.ATV.0000255309.38699.6cv1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Stannard, A. K. Articles by Zachary, I. Search for Related Content PubMed PubMed Citation Articles by Stannard, A. K. Articles by Zachary, I.

(Arteriosclerosis, Thrombosis, and Vascular Biology. 2007;27:494.)
© 2007 American Heart Association, Inc.

Vascular Biology

Vascular Endothelial Growth Factor Synergistically Enhances Induction of E-Selectin by Tumor Necrosis Factor-

Anita K. Stannard; Rohit Khurana; Ian M. Evans; Vassiliki Sofra; David I.R. Holmes; Ian Zachary

From BHF Laboratories, Department of Medicine, University College London, United Kingdom.

Correspondence to Ian Zachary, BHF Laboratories, Department of Medicine, The Rayne Building, University College London, 5 University Street, London WC1E 6JJ, United Kingdom. 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-1ß–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.

VEGF alone caused no significant induction of cell adhesion molecule expression in endothelial cells or during neointima formation in vivo. However, VEGF pretreatment enhanced E-selectin expression induced by TNF-. These results indicate that VEGF "primes" endothelial cells to enhance selective responses to proinflammatory cytokines

Key Words: cell adhesion molecules • endothelial cells • IL-1ß

This article has been cited by other articles:

				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, August 9, 2008; (2008) awn182v1. [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]