Researchers at the University of Manchester and Manchester University NHS Foundation Trust have uncovered a hidden defect in the tiny blood vessels of women with preeclampsia, a dangerous and common pregnancy complication which can threaten the lives of both mother and baby.
The breakthrough sheds new light on why blood pressure rises so dramatically in the condition and could point towards entirely new ways of treating it.
Preeclampsia affects between 2% and 8% of pregnancies worldwide and is linked to serious complications including stroke, organ damage, premature birth and stillbirth.
At present there is no cure other than delivering the baby and placenta, often forcing doctors to bring pregnancies early to protect the mother.
But now the researchers have identified a key failure in the way small arteries regulate blood flow in women with the condition.
The team recruited patients at Saint Mary's Hospital (SMH), part of MFT, and compared tiny arteries from pregnant women with and without preeclampsia. The researchers discovered that a vital natural relaxation mechanism was severely disrupted in those with the disease.
The vessels were taken from the omentum - a fold of fatty tissue inside the abdomen that helps protect and support the abdominal organs - and placed under pressure in a laboratory to study their functioning.
Healthy blood vessels rely on microscopic bursts of calcium, known as "calcium sparks", to tell the muscle in artery walls to relax and prevent excessive constriction.
But in women with preeclampsia these calcium sparks were dramatically reduced, with levels falling by as much as 75% at normal physiological pressures.
Investigating the samples at Microvascular@Manchester's, small artery research labs at UoM, led by Professor Adam Greenstein, Clinical Scientist and Consultant Geriatrician at MFT, researchers also found evidence that the cells' calcium stores were depleted and less able to refill themselves, preventing the vessels from generating the signals needed to relax properly.
This loss of an important pressure-balancing mechanism could help explain why blood vessels remain abnormally constricted in preeclampsia, driving dangerous increases in blood pressure.
The team also tested HBD2, a naturally occurring immune-system molecule that helps the body fight infection."
Although the molecule - known as a peptide - did not restore the faulty calcium sparks, it was still able to relax blood vessels by activating a different part of the same pathway.
The finding raises the possibility of future treatments that bypass the damaged mechanism altogether and directly encourage blood vessels to relax.
Researchers say such approaches could eventually help control maternal blood pressure, prolong pregnancy and reduce the need for early delivery.
Study lead author Dr Stephanie Worton from The University of Manchester, who is an Honorary Consultant in Obstetrics at the Maternal and Fetal Health Research Centre at SMH, part of MFT said: "Preeclampsia remains one of the most serious complications of pregnancy and the only definitive cure is delivery of the baby and placenta.
"Our study reveals, for the first time, a major defect in the way tiny maternal blood vessels regulate their own relaxation.
Dr Worton, who is also a researcher in the Integrative Cardiovascular Medicine Theme at the National Institute for Health and Care Research (NIHR) Biomedical Research Centre: Manchester, continued: "We found that a critical calcium signalling pathway is profoundly impaired, but also showed that blood vessels can still be relaxed through alternative mechanisms.
"These discoveries provide promising new targets for therapies aimed at controlling blood pressure and improving outcomes for mothers and babies.
"Further studies are now needed to explore whether drugs targeting these newly identified pathways could safely be developed for use during pregnancy."
The research was made possible by collaboration between the Maternal and Fetal Health Research Centre, the cardiovascular sciences research group and the MAViS (Manchester Antenatal Vascular Service) clinic, which provides specialist care for more than 300 women per year, whose pregnancies are complicated by preterm pre-eclampsia.
Professor Jenny Myers from The University of Manchester, a study author and Consultant Obstetrician at the Maternal and Fetal Health Research Centre at SMH, said: "This research demonstrates the power of collaborative research across MFT and The University of Manchester. This research, and access to human samples from women with a rare disease, is only made possible by the contribution of our research practitioners, research and specialist midwives working alongside our scientists within the university, to advance our understanding and improve care."
- The study was funded by the Tommy's Maternal and Fetal Health Research Centre, Alzheimer's Society, the British Heart Foundation and the National Institute for Health and Care Research (NIHR) Biomedical Research Centre (BRC): Manchester.
Maternal Microvascular Calcium Sparks Are Reduced in Preeclampsia is published in the journal Circulation Research https://doi.org/10.1161/CIRCRESAHA.125.327858
