Women with preeclampsia have up to 75 per cent fewer calcium sparks in small blood vessels, Manchester researchers said on Tuesday, pointing to possible new treatments.
The work was carried out by the University of Manchester and Manchester University NHS Foundation Trust, the university said, and is published in Circulation Research.
Preeclampsia affects between 2 and 8 per cent of pregnancies worldwide and is linked to serious complications including stroke, organ damage, premature birth and stillbirth.
There is no cure other than delivering the baby and placenta, which often forces doctors to bring pregnancies early to protect the mother.
The team recruited patients at Saint Mary’s Hospital, part of the trust, and compared small arteries from pregnant women with and without the condition.
The vessels were taken from the omentum, a fold of fatty tissue inside the abdomen, and placed under pressure in a laboratory to study how they worked. The analysis was done in the Microvascular@Manchester small artery research labs, led by Professor Adam Greenstein.
Healthy vessels rely on microscopic bursts of calcium, known as calcium sparks, to tell the muscle in artery walls to relax and stop them constricting too much.
In women with preeclampsia those sparks were dramatically reduced, falling by as much as 75 per cent at normal physiological pressures, against the levels seen in women without the condition.
The researchers also found evidence that the cells’ calcium stores were depleted and less able to refill, which prevented the vessels from generating the signals needed to relax properly.
They said this loss of a pressure-balancing mechanism could help explain why vessels stay abnormally constricted in preeclampsia, driving dangerous rises in blood pressure.
The team also tested HBD2, a naturally occurring immune-system molecule that helps the body fight infection. The peptide did not restore the faulty calcium sparks, but it still relaxed blood vessels by activating a different part of the same pathway.
That raises the possibility of treatments that bypass the damaged mechanism and directly encourage vessels to relax. The researchers said such approaches could eventually help control maternal blood pressure, prolong pregnancy and reduce the need for early delivery.
Lead author Dr Stephanie Worton, an honorary consultant in obstetrics at Saint Mary’s, said the study reveals “a major defect” in the way tiny maternal blood vessels regulate their own relaxation, and that it had shown vessels can still be relaxed through alternative mechanisms.
She described the findings as “promising new targets” for therapies, but said further studies are needed to establish whether drugs aimed at these pathways could safely be developed for use during pregnancy.
The research drew on collaboration between the Maternal and Fetal Health Research Centre, the cardiovascular sciences research group and the Manchester Antenatal Vascular Service clinic, which provides specialist care for more than 300 women a year whose pregnancies are complicated by preterm pre-eclampsia.
Professor Jenny Myers, a study author and consultant obstetrician, said access to human samples from women with a rare disease depends on research practitioners and specialist midwives working alongside university scientists.
The study was funded by the Tommy’s Maternal and Fetal Health Research Centre, Alzheimer’s Society, the British Heart Foundation and the NIHR Biomedical Research Centre: Manchester.