Bursting the Bubble: Pre-eclampsia Findings Challenge Previous Theories
New findings from the University of Toronto will shift the direction of future research into the mechanisms behind the most common pregnancy complication: pre-eclampsia.
Pre-eclampsia affects more than 10, 000 moms-to-be in Canada each year and its most prominent symptom is high blood pressure. Other problems associated with the condition include severe headaches, temporary vision problems, dizziness and sudden weight gain. Left untreated, pre-eclampsia is potentially fatal for mother and baby.
A team led by John Kingdom, a professor and Chair of the Department of Obstetrics and Gynaecology, discovered that in severe forms of the condition, the soluble fraction of blood — which can include the nutrients the mom supplies to her baby and the waste the baby releases — damages the blood vessel lining called endothelium. The effect isn’t seen in similar concentrations of extracellular vesicles (EVs), which are like tiny bubbles that carry cell-to-cell signals. These little ‘bubbles’ circulate throughout the body and can release their contents — micro ribonucleic acids and proteins for cell-to-cell signaling — into the cells lining the blood vessels, the endothelium.
The placenta also releases a range of particles, including EVs from the placental surface. Scientists theorize this raises blood pressure by damaging the blood vessel lining, which affects the vessels’ ability to dilate. Until now, researchers didn’t know which type of material was most damaging to the mother’s blood vessels.
“Our new data challenge the existing belief that placenta-derived micro-particles, especially EVs are to blame,” says Michelle O’Brien, lead author and a student in the Physician Assistant (PA) program. “Earlier research suggested the range of micro-particles, including EVs could potentially damage the endothelium, whereas the placenta also secretes soluble factors that promote healthy blood vessels. Our study defines the balance between these components released by the placenta into the maternal circulation. Further studies are underway to determine the what else is in the EVs.”
There hadn’t previously been any tried-and-true ways to isolate placental EVs and study their specific effects. Most research groups used variations of established methods that were better suited to isolating for larger particles.
After reviewing other research methods, the team developed a new, more efficient combination of existing methods to isolate these important carriers and determine the relative importance of soluble factors versus EVs released from the placenta into maternal circulation.
“These findings advance our knowledge of how pre-eclampsia develops,” says Kingdom. “We hope other researchers will adopt this approach to understanding the potential for the various classes of placenta-derived substances. This group includes EVs, which have the potential to either promote normal vascular function or impair it, depending on the molecular signals they carry that originated in the placenta.”
After completing her degree in Biology and Medical Science, O’Brien joined Kingdom’s lab in the placenta program at Mount Sinai Hospital, which promotes clinical and basic science research into this critical organ. While doing research with Kingdom, she met some of the PAs who work in the hospital, opening the door for O’Brien to explore a new career path.
“In Toronto, there are no obstetric PAs and I’d like to change that,” O’Brien says, noting that PAs are part of care teams in clinics and in labour and delivery units elsewhere in Ontario. “It will be a challenge, but that’s what I really want to do. There are already existing protocols in place for obstetric PAs. For example, in Hamilton, they’re an extra set of hands to support obstetricians.”
The findings are published the journal Scientific Reports. The study was supported by the Canadian Institutes of Health and Research and Alva Foundation.