Soluble VEGFR-1 secreted by endothelial cells and monocytes is present in human serum and plasma from healthy donors

被引：93

作者：

Barleon B. ^{[3
]}

Reusch P. ^{[1
]}

Totzke F. ^{[1
]}

Herzog C. ^{[1
]}

Keck C. ^{[2
]}

Martiny-Baron G. ^{[1
]}

Marmé D. ^{[1
]}

机构：

[1] Institute of Molecular Oncology, Tumor Biology Center, Freiburg

[2] Department of Obstetrics and Gynecology, University of Freiburg

[3] RELIATech GmbH, Braunschweig

来源：

Angiogenesis | 2001年 / 4卷 / 2期

关键词：

Angiogenesis; Endothelial cells; Monocytes; sVEGFR-1; VEGF;

D O I：

10.1023/A:1012245307884

中图分类号：

学科分类号：

摘要：

It was shown before that the soluble form of VEGFR-1 (sVEGFR-1) is present in serum of pregnant women. The aim of the present study was to investigate the presence of this endogenous vascular endothelial growth factor-A (VEGF-A) antagonist in human serum in more detail. sVEGFR-1 was detected in human serum and plasma from normal healthy male and female donors by ELISA. sVEGFR-1 levels ranged from non-detectable up to 440 pg/ml, with no significant difference between male and female donors. In addition, vein endothelial cells (ECs) from an intact vascular bed, the umbilical cord, were shown to secrete sVEGFR-1. Furthermore, human peripheral blood monocytes, a non-EC type expressing VEGFR-1, were shown to contribute to the sVEGFR-1 detectable in human serum and plasma for the first time. EC- and monocyte-derived sVEGFR-1 proved capable of inhibiting the VEGF induced proliferation and migration of ECs in vitro. Finally, secretion of sVEGFR-1 was increased by the angiogenic factor basic fibroblast growth factor (bFGF) in human ECs and was also enhanced in lipopolysaccharide-activated human monocytes. In human umbilical vein endothelial cells, both the membrane-bound and the sVEGFR-1 seem to be equally regulated on the mRNA as well as the protein level. The presence of an sVEGFR-1 in human serum and plasma of normal male and female donors strongly suggests that it plays an important role as a naturally occurring VEGF antagonist in the regulation and availability of VEGF-mediated biological activities in vivo.

引用

页码：143 / 154

页数：11

共 51 条

[1] Plate K.H., Breier G., Weich H.A., Risau W., Vascular endothelial growth factor is a potential tumour angiogenesis factor in human gliomas in vivo, Nature, 359, pp. 845-848, (1992)
[2] Aiello L.P., Avery R.L., Arrigg P.G., Et al., Vascular endothelial growth factor in ocular fluid of patients with diabetic retinopathy and other retinal disorders, N Engl J Med, 331, pp. 1480-1487, (1994)
[3] Fava R.A., Olson N.J., Spencer-Green G., Et al., Vascular permeability factor/endothelial growth factor (VPF/VEGF): Accumulation and expression in human synovial fluids and rheumatoid synovial tissue, J Exp Med, 180, pp. 341-346, (1994)
[4] Detmar M., Brown L.F., Claffey K.P., Et al., Overexpression of vascular permeability factor/vascular endothelial growth factor and its receptors in psoriasis, J Exp Med, 180, pp. 1141-1146, (1994)
[5] Neufeld G., Cohen T., Gengrinovitch S., Poltorak Z., Vascular endothelial growth factor (VEGF) and its receptors, FASEB J, 13, pp. 9-22, (1999)
[6] Veikkola T., Alitalo K., VEGFs, receptors and angiogenesis, Semin Cancer Biol, 9, pp. 211-220, (1999)
[7] Carmeliet P., Ferreira V., Breier G., Et al., Abnormal blood vessel development and lethality in embryos lacking a single VEGF allele, Nature, 380, pp. 435-439, (1996)
[8] Fong G.-H., Rossant J., Gertsenstein M., Breitman M.L., Role of the Flt-1 receptor tyrosine kinase in regulating the assembly of vascular endothelium, Nature, 376, pp. 66-70, (1995)
[9] De Vries C., Escobedo J.A., Ueno H., Et al., The fms-like tyrosine kinase, a receptor for vascular endothelial growth factor, Science, 255, pp. 989-991, (1992)
[10] Terman B.I., Dougher-Vermazen M., Carrion M.E., Et al., Identification of the KDR tyrosine kinase as a receptor for vascular endothelial cell growth factor, Biochem Biophys Res Commun, 187, pp. 1579-1586, (1992)

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