Evidence for the existence of a novel pregnancy-associated soluble variant of the vascular endothelial growth factor receptor, Flt-1

Banks, R. E. and Forbes, M. A. and Searle, J. and Pappin, D. and Canas, B. and Rahman, D. and Kaufmann, S. and Walters, C. E. and Jackson, A. and Eves, Paula and Linton, G. and Keen, J. and Walker, J. J. and Selby, P. J. (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. 377-386. ISSN 1360-9947

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Item Type:Article
Item Status:Live Archive

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 ~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.

Keywords:Angiogenesis; Flt-1; Pregnancy; Soluble receptor; VEGF
Subjects:C Biological Sciences > C142 Reproductive Biology
C Biological Sciences > C790 Molecular Biology, Biophysics and Biochemistry not elsewhere classified
Divisions:Professional services
ID Code:27000
Deposited On:19 Apr 2017 13:30

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