The root cause of a medical problem that endangers the lives of thousands of pregnant women and their babies in Britain each year has been discovered.
Researchers at Cambridge University have worked out what leads to pre-eclampsia, a condition that causes dangerously high blood pressure in women, often in the later stages of pregnancy.
The findings raise hope for treatments that can prevent the complication found in 2-7% of all pregnancies, which typically kills several hundred babies and six women in the UK each year. Milder forms of pre-eclampsia affect about one in 10 first-time pregnancies.
A team led by Aiwu Zhou at the Cambridge Institute for Medical Research used intense x-ray beams at the Diamond Light Source facility in Oxfordshire to study the structure of angiotensinogen, a protein linked to high blood pressure.
Scientists knew the protein triggered the release of hormones called angiotensins that cause blood vessels to constrict, but how this happened was not clear. When veins and arteries constrict, blood pressure rises in the same way that squeezing a garden hose increases the pressure of water running through it.
Zhou's team found that angiotensinogen changes shape when it is oxidised by reactive molecules in the blood. The oxidised protein bends in such a way that a common enzyme can cut it in two, releasing angiotensin. The study appears in the journal, Nature. In a follow up experiment, the researchers analysed blood samples taken from volunteers. They showed that in healthy people, a steady 60% of angiotensinogen was oxidised, but in women with pre-eclampsia the level was much higher. "When we looked at the blood samples, we were immediately able to identify eight of 12 women with pre-eclampsia," said Robin Carrell, a co-author of the study.
Professor Carrell said changes in the placenta during pregnancy alter how much oxygen the growing baby receives, but this can trigger the release of free radicals that oxidise angiotensinogen and cause blood pressure to rise.
Drugs used to treat high blood pressure, including a family of medicines called ACE inhibitors, block the later stages of the biological pathway that leads to high blood pressure. The discovery gives doctors a fresh way to target the condition. Peter Weissberg, medical director of the British Heart Foundation, which co-funded the study, said the work "offers real hope for developing strategies to prevent or treat this dangerous condition".
"Although the researchers only looked at pre-eclampsia in this study, similar strategies may be useful for those people with high blood pressure that is not effectively controlled by current medicines," Weissberg added.
Previous studies in animals support the suspicion that oxidation plays a role in pre-eclampsia. In 2006, a team led by Robin Davisson at Iowa University gave an antioxidant called tempol to pregnant mice. The drug appeared to prevent high blood pressure and halved the number of mouse pups that died before being born.
