A simple detection method for the serum sFLT1 protein in preeclampsia

Masabumi Shibuya,Tadashi Sasagawa,Haruka Matsui,Takeshi Nagamatsu

doi:10.1038/s41598-021-00152-6

Masabumi Shibuya, Tadashi Sasagawa + Show 2 more

Open Access

https://doi.org/10.1038/s41598-021-00152-6

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Journal: Scientific Reports	Publication Date: Oct 18, 2021
Citations: 4	License type: open-access

Affiliation: Jobu University, The University of Tokyo

Abstract

In normal pregnancy, the soluble form of FMS-like tyrosine kinase-1 (sFLT1)/ vascular endothelial growth factor receptor-1 (sVEGFR-1), a VEGF-trapping protein, is expressed in trophoblasts of the placenta, suggesting that it plays an important role in the physiological barrier between fetal and maternal angiogenesis, when stimulated with VEGF-A. In pathological conditions such as preeclampsia (PE), sFLT1 protein is abnormally overexpressed in trophoblasts and secreted into the serum, which could cause hypertension and proteinuria on the maternal side and growth retardation on the fetal side. Detection of an abnormal increase in serum sFLT1 during the early to middle stages of PE is essential for proper initiation of medical care. To carry out this screening for sFLT1, we developed an easier and relatively low-cost sandwich-type ELISA method using a single mixture of human serum sample with an anti-FLT1 antibody and heparin-beads, namely heparin-beads-coupled ELISA (HB-ELISA). This method takes only about 2 h, and the sFLT1 values were similar levels with commercially available recent ELISA kits: the serum sFLT1 protein was approximately 4.3-fold increased in severe PE compared with those in normal pregnancy.

Highlights

In normal pregnancy, the soluble form of FMS-like tyrosine kinase-1/ vascular endothelial growth factor receptor-1, a VEGF-trapping protein, is expressed in trophoblasts of the placenta, suggesting that it plays an important role in the physiological barrier between fetal and maternal angiogenesis, when stimulated with vascular endothelial growth factor-A (VEGF-A)
In 1993, Kendall and Thomas reported that a short FMS-like tyrosine kinase-1 (FLT1) mRNA encodes a VEGF-binding peptide that covers the 1 to 6 Ig-regions of the FLT1 with a 31 amino acid-long tail derived from intron-13, known as i13 soluble FLT1 (i13 soluble form of FMS-like tyrosine kinase-1 (sFLT1))[5,6,7]
Various types of cells such as vascular endothelial cells, macrophages in blood, podocytes in kidney, retinal neuronal cells, and trophoblasts were reported to express sFLT17,20,21. Among these sFLT1-producing cells, trophoblasts in the placenta are unique in terms of higher expression of both i13 and e15a sFLT1 and lower expression of full-length FLT113. sFLT1 is a very efficient VEGF-A/placenta growth factor (PlGF)/VEGF-B trapping molecule

Summary

Introduction

The soluble form of FMS-like tyrosine kinase-1 (sFLT1)/ vascular endothelial growth factor receptor-1 (sVEGFR-1), a VEGF-trapping protein, is expressed in trophoblasts of the placenta, suggesting that it plays an important role in the physiological barrier between fetal and maternal angiogenesis, when stimulated with VEGF-A. The sFLT1/PlGF ratio in serum was reported to be a better biomarker than sFLT1 alone for P E23–25; for this assay, two different target-oriented ELISA systems are required.

Results

Conclusion