Vascular endothelial growth factors and vascular permeability - PubMed (original) (raw)

Review

. 2010 Jul 15;87(2):262-71.

doi: 10.1093/cvr/cvq105. Epub 2010 Apr 16.

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Review

Vascular endothelial growth factors and vascular permeability

David O Bates. Cardiovasc Res. 2010.

Abstract

Vascular endothelial growth factors (VEGFs) are key regulators of permeability. The principal evidence behind how they increase vascular permeability in vivo and in vitro and the consequences of that increase are addressed here. Detailed analysis of the published literature has shown that in vivo and in vitro VEGF-mediated permeability differs in its time course, but has common involvement of many specific signalling pathways, in particular VEGF receptor-2 activation, calcium influx through transient receptor potential channels, activation of phospholipase C gamma and downstream activation of nitric oxide synthase. Pathways downstream of endothelial nitric oxide synthase appear to involve the guanylyl cyclase-mediated activation of the Rho-Rac pathway and subsequent involvement of junctional signalling proteins such as vascular endothelial cadherin and the tight junctional proteins zona occludens and occludin linked to the actin cytoskeleton. The signalling appears to be co-ordinated through spatial organization of the cascade into a signalplex, and arguments for why this may be important are considered. Many proteins have been identified to be involved in the regulation of vascular permeability by VEGF, but still the mechanisms through which these are thought to interact to control permeability are dependent on the experimental system, and a synthesis of existing data reveals that in intact vessels the co-ordination of the pathways is still not understood.

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Figures

Figure 1

Figure 1

Time course of VEGF-induced permeability. Alterations in hydraulic conductivity (Lp), solute permeability to albumin (Palb), or small solutes such as Na fluorescein (PNaF), ions (TEER) or sucrose, or sieving coefficient are shown in vivo (bold) or in vitro.

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References

    1. Senger DR, Galli SJ, Dvorak AM, Perruzzi CA, Harvey VS, Dvorak HF. Tumour cells secrete a vascular permeability factor that promotes accumulation of ascites fluid. Science. 1983;219:983–985. doi:10.1126/science.6823562. - DOI - PubMed
    1. Senger DR, Perruzzi CA, Feder J, Dvorak HF. A highly conserved vascular permeability factor secreted by a variety of human and rodent tumor cell lines. Cancer Res. 1986;46:5629–5632. - PubMed
    1. Keck PJ, Hauser SD, Krivi G, Sanzo K, Warren T, Feder J, et al. Vascular permeability factor, an endothelial cell mitogen related to PDGF. Science. 1989;246:1309–1312. doi:10.1126/science.2479987. - DOI - PubMed
    1. Folkman J. Tumor angiogenesis: therapeutic implications. N Engl J Med. 1971;285:1182–1186. - PubMed
    1. Plouet J, Schilling J, Gospodarowicz D. Isolation and characterization of a newly identified endothelial cell mitogen produced by AtT-20 cells. EMBO J. 1989;8:3801–3806. - PMC - PubMed

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