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Circ Res. 2010 Aug 6;107(3):408-17. doi: 10.1161/CIRCRESAHA.109.210963. Epub 2010 Jun 10.

VEGF blockade inhibits lymphocyte recruitment and ameliorates immune-mediated vascular remodeling.

Author information

1
Yale University School of Medicine, New Haven, Conn., USA.

Abstract

RATIONALE:

There are conflicting data on the effects of vascular endothelial growth factor (VEGF) in vascular remodeling. Furthermore, there are species-specific differences in leukocyte and vascular cell biology and little is known about the role of VEGF in remodeling of human arteries.

OBJECTIVE:

We sought to address the role of VEGF blockade on remodeling of human arteries in vivo.

METHODS AND RESULTS:

We used an anti-VEGF antibody, bevacizumab, to study the effect of VEGF blockade on remodeling of human coronary artery transplants in severe combined immunodeficient mice. Bevacizumab ameliorated peripheral blood mononuclear cell-induced but not interferon-gamma-induced neointimal formation. This inhibitory effect was associated with a reduction in graft T-cell accumulation without affecting T-cell activation. VEGF enhanced T-cell capture by activated endothelium under flow conditions. The VEGF effect could be recapitulated when a combination of recombinant intercellular adhesion molecule 1 and vascular cell adhesion molecule-1 rather than endothelial cells was used to capture T cells. A subpopulation of CD3+ T cells expressed VEGF receptor (VEGFR)-1 by immunostaining and FACS analysis. VEGFR-1 mRNA was also detectable in purified CD4+ T cells and Jurkat and HSB-2 T-cell lines. Stimulation of HSB-2 and T cells with VEGF triggered downstream ERK phosphorylation, demonstrating the functionality of VEGFR-1 in human T cells.

CONCLUSIONS:

VEGF contributes to vascular remodeling in human arteries through a direct effect on human T cells that enhances their recruitment to the vessel. These findings raise the possibility of novel therapeutic approaches to vascular remodeling based on inhibition of VEGF signaling.

PMID:
20538685
PMCID:
PMC2929975
DOI:
10.1161/CIRCRESAHA.109.210963
[Indexed for MEDLINE]
Free PMC Article

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