One in 20 first-time moms are diagnosed with pre-eclampsia, a serious complication of pregnancy for both mother and child. The symptoms are high-blood pressure and damage to kidneys and liver. There is no treatment other than early delivery of the baby. Although much is known about the symptoms, little is known about the cause.
Unravelling some of the mystery, University of Calgary researcher Jay Cross, PhD, along with a Stanford University team of investigators, has made an important finding helping to explain what leads to pre-eclampsia. The explanation appears to be a subtle but very balanced chemical dance between mother and her baby.
Cracking open mystery
“Our work has cracked open the biggest mystery in preeclampsia, its origins, that have precluded anyone from developing rational treatments,” says Cross, co-principal investigator.
The research paper titled, “Endometrial VEGF induces placental sFLT1 and leads to pregnancy complications,” will be published this month in the Journal of Clinical Investigation.
Cross is a professor in the departments of biochemistry and molecular biology, obstetrics and gynaecology, medical genetics, and comparative biology and experimental medicine and is a member of the Alberta Children’s Hospital Research Institute.
Important protein in uterus
Early in pregnancy, new blood vessels develop and evolve to efficiently send blood to the placenta. In women with pre-eclampsia, these blood vessels don't seem to develop properly.
Women with pre-eclampsia have elevated levels of a protein called sFLT1 (or soluble fms-like tyrosine kinase-1) in their blood. Too much of this protein leads to vascular problems in humans and this is thought to be because sFlt1 binds to an important vascular growth factor called VEGF.
Cross and the research team showed both in animal models and in human cells that the sFLT1 protein is induced by the growth factor coming from the mother’s uterus, an attempt by the fetus to protect itself against too much VEGF.
The discovery will change the direction of research in pre-eclampsia, as up until now, researchers believed increasing VEGF could provide a pathway to treatment. The reverse appears to be true.
The lead in this research is Nihar Nayak, PhD, who is now at Wayne State University but was with Stanford University’s School of Medicine when the study was conducted.
This is the second time in a year that the Jay Cross has collaborated with an international team. Last year, he led a research group at Cambridge University, U.K., explaining the generational effects of folate deficiency and its impact on offspring. That research was published in the prestigious journal Cell.
The work was supported by grants from the Canadian Institutes of Health Research and Alberta Innovates-Health Solutions.