Heparin promotes soluble vascular enothelial growth factor receptor expression in human placental villi: A rebuttal

摘要

We have read with very great interest the recent paper by Drewlo et al. [1]. It convincingly shows that a low molecular weight heparin (LMWH), dalteparin sodium, can induce in vitro the synthesis and release of the soluble vascular endothelial growth factor (VEGF) receptor-1 (sFLT1) by first-trimester placental villi, whereas no effect is observed on severe pre-eclampsia placental explants. The induced sFLTl concentrations quantified in LMWH-conditioned media from first-trimester placental villi were similar to those detected in severe pre-eclampsia explants. The culture media were able to induce phosphorylation profiles of the endothelial cell receptors of VEGF and placental growth factor (P1GF), VEGFR1 and VEGFR2, tested with cultured human endothelial vein endothelial cells, 'in a manner that is predicted to antagonize the actions of VEGF and P1GF at the level of the maternal vascular endothelium in vivo'. From this, it is concluded that 'use of LMWH in severe pre-eclampsia should be done with caution based on these findings, since it could exacerbate sFLT1-mediated maternal hypertension'.