A method of apheresis using vascular endothelial growth factor functionalized magnetic beads reduced levels of the soluble form of the vascular endothelial growth factor 1 in blood from women with preeclampsia, according to recent research published in the journal Hypertension.
The approach both reduces levels of the soluble form of the vascular endothelial growth factor 1 (sFlt-1) and releases placental growth factor (PlGF), which could help restore endothelial function in women with preeclampsia. The researchers said they chose sFlt-1 as a target because of “mounting evidence of its involvement in the pathogenesis of preeclampsia.” sFlt-1 has been suspected of inhibiting angiogenic signaling through “direct sequestration of angiogenic ligands” vascular endothelial growth factor (VEGF) and PlGF as well as “dominant-negative heterodimerization with surface VEGFRs.”
“During normal pregnancy, massive amounts of PlGF are produced by the placenta, reaching concentrations of free PlGF around 400 pg/mL, whereas during preeclampsia, free PlGF is extremely low due to the release of sFlt-1 into the maternal circulation,” the researchers said.
Using VEGF-functionalized magnetic beads, the researchers performed static and dynamic experiments using phosphate buffered saline (PBS), conditioned media, and plasma from women with preeclampsia. Under static conditions, there was a decrease of 33% for sFlt-1 and an increase of 27% for PlGF, while in dynamic conditions, there was a 40% decrease in sFlt-1 and a twofold increase in freed PlGF. When tested with plasma from women with preeclampsia, the ratio of sFlt-1/PlGF decreased by 63%, and VEGF release was associated with apheresis.
“This was a proof of concept study and our approach aims to restore physiologic levels of angiogenic factors,” Vassilis Tsatsaris, MD, PhD, of Cochin Hospital, Paris, said in a press release. “The reduction of sFlt-1 and the release of angiogenic factors is very significant and promising.”
Dr. Tsatsaris and his colleagues noted their next steps are to optimize the process of reducing sFlt-1 and examining how the approach works in an animal model.
“During normal pregnancy, circulating free VEGF levels are very low, almost undetectable with noncompetitive [enzyme-linked immunosorbent assay] ELISA. Whether these extremely low levels of VEGF have a physiological role during pregnancy is not known,” they wrote.
This study was funded by Agence Nationale pour la recherche, Institut Pierre Gilles de Gennes and the PremUP Foundation. One author reported receiving a grant from the Ecole Normale Supérieure and a second author reported receiving a grant from the Fondation pour la Recherche Médicale. The other authors report no relevant conflicts of interest.
SOURCE: Trapiella-Alfonso L et al. Hypertension. 2019. doi: 10.1161/HYPERTENSIONAHA.118.12380.