Activating preeclampsia could be key to developing treatment
By Graciela Gutierrez
Turning on certain protein receptors in the body has been found to induce preeclampsia, believed to be a pregnancy-induced autoimmune disease, in mouse models, say researchers at Baylor College of Medicine in Houston.
The findings, a collaboration of The University of Texas Health Science Center at Houston, Texas Children's Hospital and BCM, appear in a recent issue of Nature Medicine.
Group of symptoms
"The exact processes that cause preeclampsia in woman aren't known," said Hong (Amy) Zhang, M.D.,Ph.D., assistant professor of pathology at BCM. "The disorder manifests through a group of symptoms, most commonly high blood pressure and an abnormal amount of protein in urine."
Preeclampsia is found in about 5 percent of pregnancies, usually starting early in the third trimester. It can cause hypertension, renal functional defect, placental defects or even death. Currently there is no single reliable screening test and no well established prevention method.
Triggers
"Understanding what triggers it is important to potentially creating a treatment," Zhang added.
It was already known that women suffering from preeclampsia have a higher level of circulating autoantibody (AT1-AA) that binds and activates the angiotensin II receptor type 1a, or AT1 receptor.
Isolate antibodies
Yang Xia, Ph.D., assistant professor of biochemistry and molecular biology at UTHSC-Houston, and his research colleagues were able to isolate a group of antibodies known as immunoglobulin or IgG.
From that they were able to extract and purify AT1-AA. Pregnant mice were then injected with either the IgG or AT1-AA.
Similar symptoms in women
"Similar symptoms and pathological changes of preeclampsia found in women, such as hypertension and renal damage, were found in the mice," Zhang said.
To make sure that AT1-AA was the protein inducing the symptoms of preeclampsia, researchers co-injected losartan, an AT1 receptor antagonist or a 7 amino acid epitope peptide corresponding to the second extracellular loop of AT1 receptor with the AT1-AA to the pregnant mice. Examining the mice after the co-injection, it was found that the symptoms of preeclampsia were prevented.
New drugs needed
"While losartan worked in this mouse model, it is still too early to use as a treatment for preeclampsia. It is harmful to the baby," Zhang said. "However, seven amino acid epitope peptides may be a specific effective novel therapeutic possibility by targeting on AT1-AA in the disease. This is the first step to finding out what will work."
Zhang added, "Our hopes are to continue on this line of research to one day be able to screen for the disorder, or screen for indications that one person might be more susceptible to preeclampsia."
This work is funded by grants from the National Institutes of Health, the March of Dimes, and the Texas Higher Education Coordinating Board. The use of losartan was possible through a gift from Merck.
The paper can be found at www.nature.com/nm
