Featured Research

from universities, journals, and other organizations

Clues Into How Preeclampsia May Surface In Some Pregnancies

Date:
May 12, 2008
Source:
Beth Israel Deaconess Medical Center
Summary:
The COMT gene -- known already for its role in schizophrenia -- has been found to play a role in preeclampsia, according to a report in Nature. The study further suggests that a steroid molecule, 2-ME, may serve as both a diagnostic marker and therapeutic supplement for the treatment of this dangerous pregnancy disorder.

The COMT gene -- known already for its role in schizophrenia -- has been found to play a role in preeclampsia, according to a report in today's advance on-line issue of Nature.

Led by researchers at Beth Israel Deaconess Medical Center (BIDMC), the study further suggests that a steroid molecule, 2-ME, may serve as both a diagnostic marker and therapeutic supplement for the treatment of this dangerous pregnancy disorder.

Characterized by hypertension, proteinuria, and edema, preeclampsia affects approximately 5 percent of all pregnancies worldwide, and is a leading cause of maternal and neonatal morbidity. Knowing that placental hypoxia, or oxygen shortage, associated with vascular dysfunction, is a hallmark of the condition, senior author Raghu Kalluri, PhD and his colleagues began by screening for genes that regulate hypoxia.

"Seeing pregnant women with this disease in the clinic inspired me to dedicate our efforts to find likely causative genes that play a role in preeclampsia," says Kalluri.

"During pregnancy, hypoxia is associated with the formation of new blood vessels," explains Kalluri, Chief of the Division of Matrix Biology at BIDMC and Professor of Medicine at Harvard Medical School.

"As a result, during the first trimester of pregnancy, when the fetus is undergoing rapid development, hypoxia levels are high. As the pregnancy progresses, hypoxia levels should naturally come down as fetal blood vessels formation slows." But, he adds, for unknown reasons, patients with preeclampsia remain hypoxic well into their third trimester of pregnancy.

Studies in the Kalluri laboratory revealed an enzyme known as COMT (catechol-O-methyltransferase) in preeclampsia, a gene commonly associated with schizophrenia which, under normal circumstances, inactivates the catecholamine class of neurotransmitters.

"Interestingly, this enzyme contributes to the breakdown of estrogen into 2ME (2-methoxyestradiol), a metabolite that suppresses the activity of hypoxia inducible factor protein," explains Kalluri. "We wondered if, in cases of preeclampsia, COMT was not functioning properly. In support of this hypothesis, we found that COMT levels were deficient and 2-ME levels were lower in pregnant women with preeclampsia."

Next the investigators looked at genetically engineered COMT deficient mice; as predicted, the animals failed to produce 2-ME. At 14 weeks gestation -- the presumable equivalent of the beginning of the third trimester in human pregnancy -- the animals developed protein leak in the urine, high blood pressure and problems with placental blood vessels associated with decreased oxygen levels.

In addition, the animals delivered a day or so earlier than normal pregnant mice and there was a greater incidence of stillborn pups. However, once the pups were delivered, the health of the mother returned to normal.

"The loss of 2-ME likely sets in motion a cascade of events culminating in preeclampsia," says Kalluri. "Disruption of COMT/2-ME led to elevated hypoxia, leading to angiogenic dysfunction and placental insufficiency, which then results in a further decrease in 2-ME levels."

In the final portion of the study, the authors administered 2-ME to the mice, resulting in a reversal of preeclampsia-like-symptoms.

"Interestingly, the many diverse factors that have been identified in the recent years as elevated or suppressed in women with preeclampsia are fixed by 2-ME, suggesting that this action of COMT is central to proper vascular function in the placenta," notes Kalluri. "This study offers the possibility of screening for COMT gene defects in pregnant women to predict preeclampsia."

This research is dedicated to the memory of Dr. Judah Folkman for his inspiring contribution to this study.

This research was supported, in part, by grants from the National Institutes of Health, the British Heart Foundation and the Kanae Foundation for the Promotion of Medical Science, Japan.

Technologies associated with 2-ME/COMT and preeclampsia are licensed to Cynthus, Inc.

Study coauthors include BIDMC investigators Keizo Kanasaki, Kristin Palmsten, Hikaru Sugimoto, Yuki Hamano and Liang Xie; Shakil Ahmad of the University of Birmingham, Birmingham, UK; Samuel Parry of the University of Pennsylvania School of Medicine; Hellmut Augustin of the University of Heidelberg, Heidelberg, Germany; Vincent Gattone, Jr. of Indiana University School of Medicine; Judah Folkman of Children's Hospital Boston; and Jerome Strauss of Virginia Commonwealth University.


Story Source:

The above story is based on materials provided by Beth Israel Deaconess Medical Center. Note: Materials may be edited for content and length.


Cite This Page:

Beth Israel Deaconess Medical Center. "Clues Into How Preeclampsia May Surface In Some Pregnancies." ScienceDaily. ScienceDaily, 12 May 2008. <www.sciencedaily.com/releases/2008/05/080511190846.htm>.
Beth Israel Deaconess Medical Center. (2008, May 12). Clues Into How Preeclampsia May Surface In Some Pregnancies. ScienceDaily. Retrieved October 22, 2014 from www.sciencedaily.com/releases/2008/05/080511190846.htm
Beth Israel Deaconess Medical Center. "Clues Into How Preeclampsia May Surface In Some Pregnancies." ScienceDaily. www.sciencedaily.com/releases/2008/05/080511190846.htm (accessed October 22, 2014).

Share This



More Health & Medicine News

Wednesday, October 22, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

CDC Revamps Ebola Guidelines After Criticism

CDC Revamps Ebola Guidelines After Criticism

Newsy (Oct. 21, 2014) The Centers for Disease Control and Prevention have issued new protocols for healthcare workers interacting with Ebola patients. Video provided by Newsy
Powered by NewsLook.com
WHO: Ebola Vaccine Trials to Start a in January

WHO: Ebola Vaccine Trials to Start a in January

AP (Oct. 21, 2014) Tens of thousands of doses of experimental Ebola vaccines could be available for "real-world" testing in West Africa as soon as January as long as they are deemed safe in soon to start trials, the World Health Organization said Tuesday. (Oct. 21) Video provided by AP
Powered by NewsLook.com
First-Of-Its-Kind Treatment Gives Man Ability To Walk Again

First-Of-Its-Kind Treatment Gives Man Ability To Walk Again

Newsy (Oct. 21, 2014) A medical team has for the first time given a man the ability to walk again after transplanting cells from his brain onto his severed spinal cord. Video provided by Newsy
Powered by NewsLook.com
CDC Issues New Ebola Guidelines for Health Workers

CDC Issues New Ebola Guidelines for Health Workers

Reuters - US Online Video (Oct. 21, 2014) The U.S. Centers for Disease Control and Prevention has set up new guidelines for health workers taking care of patients infected with Ebola. Linda So reports. Video provided by Reuters
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:

Strange & Offbeat Stories


Health & Medicine

Mind & Brain

Living & Well

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins