New risk factor identified for high blood pressure during pregnancy
Preeclampsia is a serious complication of pregnancy and the major cause of death for both mother and child in Europe and the U.S. It affects about one in 20 pregnancies. The main symptoms are high blood pressure and protein in the urine. The cause of preeclampsia is still unclear. Dr. Florian Herse (Experimental and Clinical Research Center (ECRC) of the Max Delbrück Center (MDC) and the Charité), Dr. Ralf Dechend (ECRC and Helios Klinikum Berlin-Buch) and their collaborators have now identified an enzyme that is overexpressed in affected women and thus apparently contributes to development of the condition. In animal experiments, the researchers inhibited this enzyme and were able to ameliorate the disease process.
Preeclampsia originates in the placenta, which supplies the embryo/fetus in the womb with nutrients. For their study, Dr. Herse, numerous contributors, and Dr. Dechend analyzed tissue samples from 25 women diagnosed with preeclampsia and from 23 healthy pregnant women as controls. The tissue samples of the preeclamptic women were obtained from hospitals in Finland, Norway, Austria, and the U.S. that cooperated closely in the study.
Using gene-chip technology, the researchers in Berlin analyzed the expression of almost 40,000 genes. They found that in women with preeclampsia, levels of the CYP2J2 enzyme were unusually high in placental cells and the uterine lining (decidua). The placenta consists of fetal cells; the decidua, by contrast, is solely maternal tissue. The enzyme is involved in the production of specific metabolites called EETs (epoxyeicosatrienoic acids) which, among other things, regulate inflammatory processes, vascular growth, and blood pressure.
Dr. Herse and team succeeded in identifying the cells that produce the CYP2J2 enzyme as trophoblasts, which fulfill an important function in pregnancy. These fetal cells migrate from the placenta into the maternal decidua. Trophoblasts are key contributors to spiral-artery remodeling and thus ensure that the fetus is sufficiently supplied with nutrients. However, if the trophoblasts do not grow deeply enough into the decidua, this remodeling process is disturbed. As a consequence, the fetus cannot be sufficiently supplied with nutrients, leading to preeclampsia. EETs evidently have a harmful effect because they activate a substance which prevents the trophoblasts from growing into the decidua.
Both a protective and damaging effect
Previous studies indicated that EETs exert only positive effects on the cardiovascular system. EETs generally mediate vascular expansion and reduce blood pressure. They also protect the tissue from dying of oxygen deficiency. In normal pregnancies EET levels are slightly elevated.
Previous experiments with healthy pregnant rats showed that pharmacological inhibition of the CYP2J2 enzyme and the associated inhibition of EET production lead to hypertension and kidney failure. In pregnant rats with preeclamptic symptoms, however, opposite effects may occur. By inhibiting CYP2J2, the ECRC researchers were able to lower blood pressure levels in these animals.
How did these conflicting observations come about? Dr. Herse and team demonstrated that the EETs can be converted into other metabolites. A specific enzyme (cyclooxygenase, COX) alters these components further in such a way that they cause vasoconstriction and thus an increase in blood pressure. EETs that normally lower blood pressure can evidently produce metabolites that cause blood pressure to rise in preeclampsia. If however the researchers inhibited the cyclooxygenase in the pregnant animals, the EETs were not converted further and the blood pressure did not increase. "This work shows that the increased production of EET in the placenta and the conversion via cyclooxygenase into hormones that increase blood pressure both favor the development of preeclampsia," Dr. Herse and Dr. Dechend explained.
Messenger substance of the immune system apparently promotes the development of preeclampsia
But why do the bodies of women with preeclampsia produce more CYP2J2 and thus more EET? Tumor necrosis factor-alpha (TNF-alpha), a chemical messenger of the immune system, could possibly contribute. This signaling substance is released at early stages of pregnancy whenever placental blood flow is too low, causing oxygen deficiency. As the researchers showed, TNF-alpha promotes the production of CYP2J2 and EET in the placenta. In other tissues, this reaction would be useful, since EET rescues tissue from dying that has an insufficient supply of blood and therefore of oxygen. In the placenta, by contrast, this boost in production of CYP2J2 and EET could lead to a vicious circle. The trophoblasts do not grow as well into the decidua and the blood vessels and are not remodeled correctly, so that blood flow through the placenta and blood supply to the fetus deteriorates. As a consequence, the mothers becomes hypertensive and EETs under these conditions is converted in such a way that the blood pressure continues to increase.
Treatment of preeclampsia, which according to estimates costs many thousands of maternal lives across the globe every year, remains difficult. The only possibility is to induce delivery at an early stage if the clinical presentation is severe. In Germany, preeclampsia is the cause for up to 20,000 premature births annually. Once the child is born, the symptoms subside in the mother. Nevertheless, she may suffer long-term increased risk for cardiovascular disease and develop heart attack, stroke, or hypertension at an early age. For the child, depending on the stage of fetal development, the premature birth may result in death or severe lifelong disability, and the child may also have an increased risk for cardiovascular disease later on. The research conducted by Dr. Herse, the entire team, and Dr. Dechend implicates a previously unknown mechanism. Their discovery may contribute to a better understanding of the disease process and its causes, and may ultimately aid in developing a therapy.
More information: CYP2J2 expression and circulating epoxyeicosatrienoic metabolites in preeclampsia, DOI: 10.1161/CIRCULATIONAHA.112.127340
Provided by Helmholtz Association of German Research Centres
- New finding may help explain development of preeclampsia Feb 08, 2008 | not rated yet | 0
- Battle between the placenta and uterus could help explain preeclampsia Oct 11, 2011 | not rated yet | 0
- New study could lead to preeclampsia prevention Nov 06, 2012 | not rated yet | 0
- Tracing the molecular causes of preeclampsia Sep 10, 2012 | not rated yet | 0
- Researchers identify key contributor to pre-eclampsia Sep 04, 2009 | not rated yet | 0
- Motion perception revisited: High Phi effect challenges established motion perception assumptions Apr 23, 2013 | 3 / 5 (2) | 2
- Anything you can do I can do better: Neuromolecular foundations of the superiority illusion (Update) Apr 02, 2013 | 4.5 / 5 (11) | 5
- The visual system as economist: Neural resource allocation in visual adaptation Mar 30, 2013 | 5 / 5 (2) | 9
- Separate lives: Neuronal and organismal lifespans decoupled Mar 27, 2013 | 4.9 / 5 (8) | 0
- Sizing things up: The evolutionary neurobiology of scale invariance Feb 28, 2013 | 4.8 / 5 (10) | 14
Pressure-volume curve: Elastic Recoil Pressure don't make sense
17 hours ago From pressure-volume curve of the lung and chest wall (attached photo), I don't understand why would the elastic recoil pressure of the lung is...
If you became brain-dead, would you want them to pull the plug?
May 17, 2013 I'd want the rest of me to stay alive. Sure it's a lousy way to live but it beats being all-the-way dead. Maybe if I make it 20 years they'll...
MRI bill question
May 15, 2013 Dear PFers, The hospital gave us a $12k bill for one MRI (head with contrast). The people I talked to at the hospital tell me that they do not...
Ratio of Hydrogen of Oxygen in Dessicated Animal Protein
May 13, 2013 As an experiment, for the past few months I've been consuming at least one portion of Jell-O or unflavored Knox gelatin per day. I'm 64, in very...
Alcohol and acetaminophen
May 13, 2013 Edit: sorry for the typo in the title , can't edit I looked around on google quite a bit and it's very hard to find precise information on the...
Marie Curie's leukemia
May 13, 2013 Does anyone know what might be the cause of Marie Curie's cancer
- More from Physics Forums - Medical Sciences
More news stories
In 2008 researchers from the University of Southern Denmark showed that the drug thioridazine, which has previously been used to treat schizophrenia, is also a powerful weapon against antibiotic-resistant bacteria such as ...
Medical research May 17, 2013 | 3.7 / 5 (3) | 0 |
Scientists investigating the interaction of a group of proteins in the brain responsible for protecting nerve cells from damage have identified a new target that could increase cell survival.
Medical research May 17, 2013 | 5 / 5 (1) | 0
New findings by researchers carrying out experiments at the U.S. Department of Energy Office of Science's Advanced Photon Source (APS) help explain why some drugs that interact with two kinds of human serotonin ...
Medical research May 17, 2013 | not rated yet | 0 |
Peptide molecules derived from the body's natural immune system can help boost the body's defence against life-threatening blood poisoning, joint University research has uncovered.
Medical research May 17, 2013 | 4 / 5 (1) | 0 |
A new Montréal study conducted by Dr. May Faraj, associate research professor at the Université de Montréal and invited scientist at the IRCM, along with her research team and medical collaborators, shows ...
Medical research May 17, 2013 | not rated yet | 0 |
11 hours ago | not rated yet | 0 |
The latest makeover to a massive psychiatric tome honored by some, reviled by others and even called the "Bible" of mental disorders is being released Saturday with a host of new changes.
8 hours ago | not rated yet | 0
A new case of the deadly coronavirus has been detected in Saudi Arabia where 15 people have already died after contracting it, the health ministry announced on Saturday on its Internet website.
8 hours ago | not rated yet | 0
19 hours ago | 5 / 5 (1) | 0
20 hours ago | 5 / 5 (1) | 0 |
A ground-breaking advance in colonoscopy technology signals the future of colorectal care, according to research presented today at Digestive Disease Week(DDW). Additional research focuses on optimizing the minimal withdrawal ...
10 hours ago | 5 / 5 (2) | 0