Roughly one in 20 women develops preeclampsia during pregnancy, a high blood pressure condition that can be life-threatening to both mother and baby. The disease is characterized by a massive increase in sFlt-1 (the soluble form of the vascular endothelial growth factor 1), which is released by the placenta into the maternal bloodstream. It is this growth factor that causes blood vessel wall dysfunction by binding two important angiogenic molecules that are responsible for maintaining healthy blood vessel walls. These molecules are endogenous PIGF (placental growth factor) and VEGF (vascular endothelial growth factor). A new proof-of-concept study has now shown that magnetic beads functionalized with VEGF as a “competitive” ligand can selectively capture sFlt-1 and reduce its level in blood by 40%, thus freeing up endogenous PIGF and VEGF so they can do their job.
Preeclampsia leads to high blood pressure and kidney disfunction and the condition affects an estimated 6-8% of pregnant women in the US. It can cause severe complications for the mother (such as seizures, stroke, renal failure and liver problems) and the baby (low birth weight, preterm delivery and even stillbirth). There is currently no cure for the disease.
One way to reduce the concentration of sFlt-1 in the bloodstream is to capture it in a technique called extracorporeal apheresis. Indeed, researchers have recently shown that columns made of materials like dextran sulphate can reduce sFlt-1 concentrations by 18% in blood samples of women with preterm preeclampsia. This strategy is nonspecific, however, and may have its own potential adverse effects because it not only binds sFlt-1 but many other molecules too.
Competitive biomimetic approach
Researchers in France have now developed a specific apheresis approach to restore a healthy physiological angiogenic balance.
In their experiments, they grafted magnetic beads with ligands of SFlt-1, which competes with PIGF in blood. To increase the capture of sFlt-1 over PIGF, they chose to use VEGF as a competitive ligand that has a ten times greater affinity for sFlt-1 than does PIGF. This competitive biomimetic approach thus captures circulating sFlt-1 while releasing endogenous PIGF, thereby increasing the amount of bioavailable PIGF, they say.
The team proved that its technique worked by integrating it into a microfluidic device that mimics real apheresis. It found that the magnetic beads decreased sFlt-1 by 40% and freed up two times more PIGF, reducing the sFlt-1/PIGF ratio by 63% in the blood plasma of preeclamptic patients.
Wearable patch measures central blood pressure
Towards in vivo animal tests
“This was a proof-of-concept study and our approach aims to restore physiological levels of angiogenic factors,” says study lead author Vassilis Tsatsaris, who is a professor of obstetrics and gynaecology at Cochin Hospital in Paris. “The reduction of sFlt-1 and the release of angiogenic factors is very significant and promising.”
The researchers, reporting their work in Hypertension, say that they would now like to optimize the grafting process and develop apheresis columns based on their technique. They would then like to test out the technique in animals in vivo.
Hypertension is published by the American Heart Association and this research was funded by the French National Agency for Research.
