Mutations of a gene can be the cause of complications of preeclampsia
Researchers from the University of Miami (UM) School of Medicine demonstrated with a model tested in mice that many complications associated with preeclampsia, a disease that affects pregnant women, are caused by mutations in a gene called GSNOR.
The importance of this finding, which was echoed on Tuesday by the specialized Journal of the American Heart Association, is that it opens a new way to develop treatments for preeclampsia, a disease whose incidence is higher in African-American women in the US. Hispanics.
“Medicine has made little or no progress in understanding and treating preeclampsia and that is reflected in a high rate of mortality and complications among mothers and newborns,” said Joshua Hare, principal investigator of the study and director of the Institute. Interdisciplinary Stem Cell Program at the UM Miller School of Medicine.
Preeclampsia causes high blood pressure in pregnant women, especially in the third trimester, and in some cases causes organ damage, leading to increased mortality in mothers and babies, as well as premature births.
Additionally, some women face elevated cardiovascular risks for years after their pregnancies.
Although preeclampsia is a complex disease, the study found that at least one potential cause is quite simple: a problem in the GSNOR gene, notes a statement from the Miller School.
Many enzymes undergo a binding process with a nitric oxide molecule (nitrosylation) which increases their activity.
What the GSNOR mutations do is remove the nitric oxide molecules from those enzymes, thereby returning them to a less active state.
When defects in the gene impair GSNOR function or remove the protein entirely, they can lead to high blood pressure and other effects associated with preeclampsia.
IN SEARCH OF BIOMARKERS
Using a GSNOR-deficient mouse model has provided researchers with the opportunity to investigate the disease, identify biomarkers and test potential treatments, the statement said.
To help validate their discovery, the team collected human placentas from preeclampsia patients at a University of Miami hospital, Jackson Memorial.
Further analysis showed that these women also experienced a loss of GSNOR, and the team is now continuing to study these placentas to identify biomarkers that may help develop a treatment.
Another goal is to determine the mechanisms that may be driving higher mortality in minority communities in the country due to preeclampsia.
“Hispanic and African-American populations have a higher incidence of preeclampsia. This has been well established, but we really don’t know why,” said Shathiyah Kulandavelu, a research assistant professor in the Miller School Department of Pediatrics and the paper’s first author.
In addition to identifying the role of GSNOR in preeclampsia, the researchers also tested a possible treatment and showed that large doses of vitamin C relieved symptoms in the mice used in their research.
However, the authors caution that this approach may not be effective in human patients. In fact, vitamin C has failed to treat preeclampsia in clinical trials.
“When we look at preeclampsia, we find that there are many different subtypes. So there could be women with a variety of causes, including increased inflammation, oxidative stress, or a genetic disorder, as well as problems with nitrosylation,” Kulandavelu said.