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
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.
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页码:143 / 154
页数:11
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