Preeclampsia, the most common pregnancy complication, is a condition in which there is a sudden, sharp rise in blood pressure, there is also swelling and excess protein albumin in urine (albuminuria). Preeclampsia is the major cause of death for both the pregnant mother and child in the USA and Europe.
Approximately one in every 20 pregnant women develops preeclampsia. Dr. Florian Herse, Dr. Ralf Dechend and team explained that CYP2J2, an enzyme, is overexpressed in affected females and appears to be a contributory factor to the development of preeclampsia.
They explained in the journal Circulation that when the enzyme was inhibited in animal experiments, their preeclampsia symptoms improved.
Preeclampsia starts off in the placenta, which provides the growing baby with essential nutrients and oxygen. The scientists analyzed tissue samples from 25 women who had been diagnosed with preeclampsia, as well as 23 other "healthy" pregnant females (controls). Tissue samples were obtained from hospitals in the USA, Austria, Norway and Finland.
They used chip technology to analyze the expression of nearly 40,000 genes. Among all the women with preeclampsia, they found unusually high levels of the CYP2J2 enzyme in the decidual and placental cells. The decidua consists solely of maternal cells (the placenta has fetal cells).
CYP2J2 is involved in the production of EETs (epoxyeicosatrienoic acids), specific metabolites which are involved in the regulation of inflammatory processes, blood pressure and vascular growth.
The team managed to identify the cells that produce the CYP2J2 enzyme as trophoblasts, which have a vital function during pregnancy. These fetal cells migrate from the placenta into the maternal decidua.
Trophoblasts contribute to spiral-artery remodeling, making sure the fetus has an adequate supply of nutrients. This remodeling process is undermined if the trophoblasts do not grow deeply enough into the decidua, resulting in an inadequate supply of nutrients to the fetus, and eventually preeclampsia.
EETs are harmful because they activate a substance which stops the trophoblasts from growing into the decidua.
EETs protect and also damage health
According to prior studies, EETs are good for the cardiovascular system. They mediate vascular expansion and lower blood pressure, as well as protecting the tissue from dying of oxygen deprivation. EET levels are slightly elevated in healthy pregnancies.Experiments with healthy pregnant rats had shown that the inhibition of the CYP2J2 enzyme, and the resulting inhibition of EET production, resulted in hypertension and kidney failure. However, the opposite occurred with rats with preeclampsia. The inhibition of CYP2J2 resulted in lower blood pressure among the lab rats with preeclampsia.
How did the team find out about these two conflicting effects on health?
The team showed that EETS may be converted into other metabolites. COX (cyclooxygenase), an enzyme, further alters these components so that they cause the blood vessels to constrict, resulting in hypertension.
EETs that would normally bring blood pressure down can evidently produce metabolites that have the opposite effect in preeclampsia. However, if pregnant animals had their cyclooxygenase inhibited, the EETs were not further converted, which in turn stopped blood pressure from rising.
Dr. Herse and Dr. Dechend wrote:
"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."
Why does a preeclampsia woman's body produce more EET?
Substances in the immune system appear to encourage the development of preeclampsia, but why do women with preeclampsia produce more CYP2J2, and the resulting higher levels of EET? TNF-alpha (tumor necrosis factor-alpha), a chemical messenger of the immune system, may contribute to higher CYP2J2 levels.TNF-alpha is released early on during pregnancy when placental blood flow drops and causes oxygen deficiency.
The scientists showed that TNF-alpha promotes CYP2J2 production and EET in the placenta. This reaction would be beneficial in non-placental tissue, because EET saves oxygen-starved tissue from dying by increasing blood flow. The authors explained that "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 mother becomes hypertensive and EETs under these conditions is converted in such a way that the blood pressure continues to increase."
Preeclampsia causes many thousands of deaths each year around the world. The only effective treatment is to induce early delivery of the baby if symptoms are severe.
Up to 20,000 premature births occur annually in Germany because of preeclampsia. As soon as the mother has given birth, her preeclampsia symptoms subside. However, a mother who had preeclampsia may be at a higher risk for heart attack, stroke, or early-age hypertension over the long-term. A study carried out by researchers from Ben-Gurion University found that women with preeclampsia have a higher long-term risk of hospitalization.
Being born very prematurely significantly increases the risk of lifelong disability or early death for the child, as well as cardiovascular disease later on in life.
The researchers say their discovery could help specialists better understand the process and causes of preeclampsia, which in turn may assist in the discovery of effective therapies for the disease.
In an Abstract in Circulation, the authors concluded:
"Our data implicate CYP2J2 in the pathogenesis of preeclampsia and as a potential candidate for the disturbed uteroplacental remodeling, leading to hypertension and endothelial dysfunction."
Studies have found that:
- Autoimmune genes are associated with preeclampsia risk.
- Women with preeclampsia have a lower long-term risk of developing breast cancer.
- Traffic pollution increases preeclampsia risk.
- Exercise before and during early pregnancy may help reduce preeclampsia risk.
Source:MNT
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