Soluble VEGFR-1 secreted by endothelial cells and monocytes is present in human serum and plasma from healthy donors.
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.
Barleon
B
B
RELIATech GmbH, Mascheroderweg 1b, D-38124 Braunschweig, Germany. Bernhard.Barleon@reliatech.de
Reusch
P
P
Totzke
F
F
Herzog
C
C
Keck
C
C
Martiny-Baron
G
G
Marmé
D
D
D001483:Base Sequence; D002478:Cells, Cultured; D017931:DNA Primers; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D008297:Male; D009000:Monocytes / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D020794:Receptor Protein-Tyrosine Kinases / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D040281:Vascular Endothelial Growth Factor Receptor-1
D017931:DNA Primers; D011518:Proto-Oncogene Proteins; D020794:Receptor Protein-Tyrosine Kinases; D040281:Vascular Endothelial Growth Factor Receptor-1