Despite being a topic of greater interest for an entire century, it has not been clear how preeclampsia develops – so far.
Researchers believe they have now discovered the main cause of preeclampsia.
We found a missing piece on the puzzle. Cholesterol crystals are the key and we are the first to bring this to light. “
Gabriela Silva, Researcher
Silva works at the University of Norway (NTNU) Center for Excellence Molecular Inflammation Research Center (NEMIR), where she is part of a research group for inflammation in pregnancy led by Professor Ann-Charlotte Iversen.
More efficient treatment possible
The findings are good news for about three per cent of pregnant women in Norway who get this disease. Worldwide, preeclampsia is a leading cause of illness and death in both mother and fetus.
In preeclamptic pregnancy, the placenta does not develop properly, and sometimes the baby receives too little nutrition.
The symptoms of preeclampsia are often mild, but in some cases the condition is so severe that the baby has to be delivered too soon.
Preeclampsia does not disappear until the baby is born. Since no one has understood why the condition is occurring, the routine treatment is to monitor and reduce the symptoms.
Silva believes that future treatment will now be more effective.
Cholesterol tested in uterine and placenta wall
“Pregnancy is indeed a kind of natural inflammatory condition, and in the case of preeclampsia, the inflammation has become too strong and leads to infection,” Silva says.
Women with preeclampsia are at greater risk of developing cardiovascular disease later in life.
It was only this connection that led the researchers to choose to study cholesterol in pregnant women with preeclampsia. Cholesterol is a major cause of cardiovascular disease.
Cholesterol crystals are found in plaque that clog blood vessels. The crystals are formed when bad cholesterol accumulates in the walls of the blood vessel. Studies have shown that cholesterol crystals are particularly powerful starters of inflammation in the body and can clog the bloodstream.
When the immune response runs wild
Cholesterol crystals are identified as harmful substances in the body that need to be cleansed. But the incoming immune cells are unable to break down the work. They want consolidation, and more immune cells come in, useless. The immune response runs wild, and the inflammatory process worsens.
Silva found that inflammation was highest in the region known as the maternal-fetal interface, where maternal cells come into direct contact with fetal cells. This occurs in the placenta and uterine wall.
“This direct contact means that the inflammation directly affects the communication between mother and fetus and contributes to even greater inflammation in the mother,” says Silva.
Pregnant women have high cholesterol levels
Cholesterol levels are high in all pregnant women, because both the fetus and the placenta need cholesterol. But rates were even higher in women with preeclampsia. They also had a lot more bad cholesterol, which is the type of cholesterol found in people at high risk for cardiovascular disease.
Silva went to great lengths to solve the puzzle. She used print samples from a biobank picked up by the CEMIR research group, and included placenta samples from 90 women with preeclampsia obtained immediately after birth. The researchers therefore had tension samples from both the uterine wall and placenta. The samples were examined using advanced microscopes.
It took years of research to reach the result.
Women who are at risk should lower their cholesterol
Future treatments for preeclampsia may include cholesterol-lowering medications, such as statins, but more research is needed to clarify their effects.
“Some women are at greater risk of preeclampsia from the beginning. They should have a cholesterol test. This is not done regularly today, but should be done regularly in the future. The use of statins is not during pregnancy is now recommended, but several clinical studies take a closer look at this and show that pravastatin, for example, can be safe to use during pregnancy, “says Silva.
Source:
Norwegian University of Science and Technology (NTNU)
Magazine Reference:
Silva, GB, et al. (2020) Cholesterol crystals and NLRP3 mediated inflammation in the uterine wall Decidua in normal and preeclamptic pregnancy. Boundaries of Immunology. doi.org/10.3389/fimmu.2020.564712.