New enzyme that contributes to preeclampsia has been discovered

New enzyme contributes to Preeclampsia

Preeclampsia is one of the most feared complications that can occur during pregnancy and can affect both the mother and child ‘s health. Although many studies have been performed on this condition, the  causes of this disease could not be clearly identified. But now researchers at the Experimental and Clinical Research Center (ECRC) of the Max Delbrück Center have made new discoveries on the triggers of preeclampsia.
Preeclampsia consists of hypertension (that is blood pressure values above 140/90 mmHg) and proteinuria, which means proteins in the urine. Although this condition can be controlled with antihypertensive medications, there are emergency situations where the only solution is Cesarean section.

Preeclampsia Treatment

The researchers found that an enzyme called CYP2J2 is high in women with preeclampsia and that this enzyme is the basis of this condition. This idea is supported by the fact that experiments on animals have shown that by inhibiting this enzyme, preeclampsia symptoms are relieved.
To reach these conclusions, the researchers conducted a study that included 48 women: 25 women diagnosed with preeclampsia and 23 healthy women from Finland, Norway, Austria, and the U.S.

After approximately 40,000 genes analyzed, it was found that expression of CYP2J2 enzyme is found in high levels in placental cells and the uterine lining (decidua) of women with preeclampsia. It seems that this enzyme is involved in the production of specific metabolites called EETs (epoxyeicosatrienoic acids), which leads to hypertension. In addition to hypertension, these metabolites play a role in inflammatory processes and vascular growth.

In addition, the team of researchers led by Dr. Herse  and Dr. Dechend found that the cells that produce this enzyme are the trophoblasts. Trophoblasts, fetal cells that migrate from the placenta in maternal decidua, contribute to the remodeling of spiral-arteries that nourish the fetus with nutrients. But if these trophoblasts are not well implanted into the decidua, then blood flow is disturbed and so preeclampsia occurs. According to the findings so far, EETs prevent normal implantation of  trophoblasts in decidua.

Previous studies done on rats have shown that in healthy pregnant mice, inhibiting the enzyme and the EET leads to hypertension and kidney failure. What is interesting is that in mice with preeclampsia, by inhibiting the same enzyme, there are adverse effects. In other words, CYP2J2 enzyme inhibition causes a  decrease in blood pressure. The explanation is that EETs are converted to other metabolites. Also an increasingly important role in this mechanism is played by TNF-alpha that promotes the production of CYP2J2 and EET in the placenta.