Banks, R. E., Forbes, M. A., Searles, J., Pappin, D., Canas, B., Rahman, D., Kaufmann, S., Walters, C. E., Jackson, A., Eves, P., Linton, G., Keen, J., Walker, J. J., Selby, P. J. (April 1998) Evidence for the existence of a novel pregnancy-associated soluble variant of the vascular endothelial growth factor receptor, Flt-1. Molecular Human Reproduction, 4 (4). pp. 377-86. ISSN 1360-9947 (Print)1360-9947 (Linking)
Abstract
Angiogenesis is essential in physiological processes including ovulation, implantation and pregnancy. One of the most potent regulators is the cytokine vascular endothelial growth factor (VEGF). We provide evidence for a novel pregnancy-associated soluble variant of the VEGF receptor Flt-1. VEGF ranged from undetectable to 157.3 pg/ml (mean 49.9 pg/ml, SD 48.4 pg/ml) in plasma samples from normal volunteers (n = 10), but was undetectable in plasma from pregnant women (n = 12) and amniotic fluid (n = 10). Recoveries of spiked VEGF were poor in pregnancy-related samples, indicating the presence of VEGF-binding activity which was confirmed using biosensor and chromatographic techniques. Partial purification and protein sequencing indicated a novel soluble form of Flt-1 with a subunit size of 150 kDa. Normally present as a multimeric structure of approximately 400-550 kDa, complexes of 600-700 kDa were formed following binding of multiple VEGF molecules. Reverse transcriptase polymerase chain reaction of Flt-1 in placenta, amnion, chorion, human umbilical vein endothelial cells and cord blood samples produced bands of the predicted sizes but failed to identify any additional RNA species, and possible reasons for this are discussed. Soluble Flt-1 may be important in regulating the actions of VEGF in angiogenesis and trophoblast invasion and may have therapeutic implications in diseases with inappropriate angiogenesis such as proliferative retinopathies and cancer.
| Item Type: | Paper |
|---|---|
| Additional Information: | Banks, R E Forbes, M A Searles, J Pappin, D Canas, B Rahman, D Kaufmann, S Walters, C E Jackson, A Eves, P Linton, G Keen, J Walker, J J Selby, P J Research Support, Non-U.S. Gov't England Molecular human reproduction Mol Hum Reprod. 1998 Apr;4(4):377-86. |
| Uncontrolled Keywords: | Amino Acid Sequence Endothelial Growth Factors/blood/metabolism Female Fetal Blood Humans Lymphokines/blood/metabolism Male Molecular Sequence Data Molecular Weight Placenta Pregnancy Protein Binding Proto-Oncogene Proteins/ chemistry/ isolation & purification Receptor Protein-Tyrosine Kinases/ chemistry/ isolation & purification Solubility Umbilical Veins/cytology Vascular Endothelial Growth Factor A Vascular Endothelial Growth Factor Receptor-1 Vascular Endothelial Growth Factors |
| Subjects: | diseases & disorders > cancer > angiogenesis organs, tissues, organelles, cell types and functions > cell types and functions > cell types organs, tissues, organelles, cell types and functions > cell types and functions > cell types organs, tissues, organelles, cell types and functions > cell types and functions > cell types organism description > animal > developmental stage > fetal bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein receptor |
| CSHL Authors: | |
| Communities: | CSHL labs > Pappin lab |
| Depositing User: | Kathleen Darby |
| Date: | April 1998 |
| Date Deposited: | 05 May 2014 13:55 |
| Last Modified: | 05 May 2014 13:55 |
| Related URLs: | |
| URI: | https://repository.cshl.edu/id/eprint/29873 |
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