The breakthrough sheds new light on the dramatic rise in blood pressure associated with pre-eclampsia and could lead to entirely new treatment approaches. The condition affects between two and eight per cent of pregnancies globally and is linked to severe complications such as stroke, organ damage, premature birth, and stillbirth.
Currently, the only definitive cure for pre-eclampsia is the delivery of the baby and placenta, often necessitating early induction of labour. The research team, which recruited patients from Saint Mary’s Hospital (part of MFT), discovered that a crucial natural relaxation mechanism in small arteries was severely disrupted in women with the condition.
Tiny arteries, taken from the omentum (a fatty tissue fold in the abdomen), were studied in a laboratory. Healthy blood vessels use microscopic bursts of calcium, known as “calcium sparks”, to signal artery walls to relax and prevent excessive constriction. However, in women with pre-eclampsia, these calcium sparks were dramatically reduced, falling by as much as 75 per cent.
Further investigation at the University of Manchester's small artery research labs, led by Professor Adam Greenstein, revealed that the cells' calcium stores were depleted and less able to refill, hindering the vessels' ability to generate the relaxation signals. This loss of a pressure-balancing mechanism may explain the abnormal blood vessel constriction and dangerous blood pressure increases seen in pre-eclampsia.
The study also explored HBD2, a naturally occurring immune-system molecule. While it did not restore the faulty calcium sparks, it was able to relax blood vessels by activating a different part of the same pathway. This suggests potential future treatments that could bypass the damaged mechanism and directly encourage blood vessel relaxation, potentially helping to prolong pregnancies and reduce early deliveries.
“"Our study reveals, for the first time, a major defect in the way tiny maternal blood vessels regulate their own relaxation. 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."
Dr Stephanie Worton, from The University of Manchester, highlighted that further studies are needed to explore the development of drugs targeting these pathways for use during pregnancy. The research was a collaboration between the Maternal and Fetal Health Research Centre, the cardiovascular sciences research group, and the MAViS clinic, which provides specialist care for women with preterm pre-eclampsia.
Professor Jenny Myers, a study author and Consultant Obstetrician at the Maternal and Fetal Health Research Centre at SMH, emphasised the power of collaborative research between MFT and The University of Manchester, noting the importance of access to human samples and the contributions of research practitioners, midwives, and scientists.
The study, titled “Maternal Microvascular Calcium Sparks Are Reduced in Preeclampsia”, 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: Manchester. It is published in the journal Circulation Research.
