Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Researchers identify protein associated with severe preeclampsia

06.06.2006
Study finds that the endoglin protein acts together with sFlt1 to rapidly escalate disease

Building on their earlier discovery which found that elevated levels of the sFlt1 placental protein leads to the onset of preeclampsia, researchers at Beth Israel Deaconess Medical Center (BIDMC), in collaboration with a research team from The Hospital for Sick Children, Toronto, have identified a second protein which, in combination with sFlt1, escalates preeclampsia to a severe – and life-threatening -- state.

These new findings, reported in the June 4, 2006 on-line issue of Nature Medicine, provide another critical piece of information about this puzzling disease, which complicates five percent of all pregnancies worldwide and is a major cause of maternal and fetal mortality, particularly in developing nations.

"Preeclampsia typically develops in the third trimester of pregnancy and is characterized by high blood pressure, edema and protein in the urine," explains the study’s senior author S. Ananth Karumanchi, MD, a nephrologist in the Center for Vascular Biology at BIDMC and Assistant Professor of Medicine, Obstetrics and Gynecology at Harvard Medical School.

Three years ago, Karumanchi and his colleagues demonstrated that the placenta plays a central role in the course of these events, and that elevated levels of a placental protein called sFlt1 (soluble fms-like tyrosine kinase) are key to the onset of the disease.

However, for unknown reasons, a subset of preeclampsia patients will go on to experience severe preeclampsia – a group of dramatically escalated symptoms characterized by a sudden, massive rise in blood pressure, which can lead to the onset of seizures, as well as the development of fetal growth restriction and the HELLP syndrome. HELLP, which stands for hemolysis, elevated liver enzymes and low platelets, indicates that the mother’s liver and blood-clotting systems are not functioning properly, and the health of both mother and infant are in serious danger.

"During the course of our previous experiments [to confirm the role of sFlt1 in the disease] we observed that although all of the animals treated with sFlt1 exhibited telltale symptoms of hypertension and proteinuria, they did not all go on to develop symptoms of the HELLP syndrome," notes Karumanchi.

"We, therefore, hypothesized that other placenta-derived proteins must be acting jointly with sFlt1 to induce vascular damage and escalate the disease to its severe form."

Using microarray analysis of human placental specimens from patients with preeclampsia, Karumanchi and his coauthors observed that a protein known as endoglin was significantly upregulated. (Endoglin was discovered 20 years ago in the laboratory of study collaborator Michelle Letarte at The Hospital for Sick Children, Toronto.) A co-receptor for transforming growth factor beta family proteins, endoglin is expressed on endothelial cells lining the blood vessels, and thereby plays an important role in maintaining the health and integrity of the vascular system.

"Our further investigations revealed that the extracellular region of the endoglin protein is shed into maternal circulation," explains Karumanchi. "We discovered that this shed form -- referred to as ’soluble endoglin’ – was circulating in very high quantities among women with severe forms of preeclampsia."

In order to understand the protein’s biological role, the investigators next administered soluble endoglin to pregnant rats; their results showed that this protein was indeed amplifying the vascular damage mediated by sFlt1, resulting in the symptoms of severe preeclampsia.

"What is apparently happening is that both sFlt1 and soluble endoglin are inhibiting the functions of two angiogenic growth factors – vascular endothelial growth factor [VEGF] and transforming growth factor beta," explains Karumanchi. "The diminished signaling of these growth factors in the vasculature adversely affects the health of the mother’s small blood vessels." The result is the onset of severe preeclampsia and its dangerous consequences for both mother and infant.

"We believe that these latest findings will have important diagnostic and therapeutic implications for the management of this disease," says Karumanchi.

Adds Benjamin Sachs, MBBS, DPH, Chief of the Department of Obstetrics and Gynecology at BIDMC, "Preeclampsia affects 200,000 pregnancies a year in the United States and often leads to premature births. Severe preeclampsia is one of the world’s leading causes of maternal and fetal mortality and poses a particular risk to women in developing countries. This new information provides us with another key piece of evidence as we work toward developing the means to diagnose, and eventually treat, this disease."

Study coauthors include BIDMC investigators Shivalingappa Venkatesha, PhD, Chun Lam, MD, Jun-ichi Hanai, MD, PhD, Tadanori Mammoto, MD, PhD, Yuval Bdolah, MD, Kee-Hak Lim, MD, Hai-Tao Yuan, MD, Towia Libermann, PhD, Isaac Stillman, MD, Franklin Epstein, MD, Frank Sellke, MD, PhD, and Vikas Sukhatme, MD, PhD; Mourad Toporsian, PhD, and Michelle Letarte, PhD, of The Hospital for Sick Children, University of Toronto, Ontario, Canada; Yeon Kim, MD, and Roberto Romero, MD, of the National Institute of Child Health and Human Development, Bethesda, Maryland; Drucilla Roberts, MD, PhD, of Massachusetts General Hospital; and Patricia D’Amore, PhD, of Schepens Eye Research Institute, Boston.

Bonnie Prescott | EurekAlert!
Further information:
http://www.bidmc.harvard.edu

More articles from Life Sciences:

nachricht Meadows beat out shrubs when it comes to storing carbon
23.11.2017 | Norwegian University of Science and Technology

nachricht Migrating Cells: Folds in the cell membrane supply material for necessary blebs
23.11.2017 | Westfälische Wilhelms-Universität Münster

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Frictional Heat Powers Hydrothermal Activity on Enceladus

Computer simulation shows how the icy moon heats water in a porous rock core

Heat from the friction of rocks caused by tidal forces could be the “engine” for the hydrothermal activity on Saturn's moon Enceladus. This presupposes that...

Im Focus: Nanoparticles help with malaria diagnosis – new rapid test in development

The WHO reports an estimated 429,000 malaria deaths each year. The disease mostly affects tropical and subtropical regions and in particular the African continent. The Fraunhofer Institute for Silicate Research ISC teamed up with the Fraunhofer Institute for Molecular Biology and Applied Ecology IME and the Institute of Tropical Medicine at the University of Tübingen for a new test method to detect malaria parasites in blood. The idea of the research project “NanoFRET” is to develop a highly sensitive and reliable rapid diagnostic test so that patient treatment can begin as early as possible.

Malaria is caused by parasites transmitted by mosquito bite. The most dangerous form of malaria is malaria tropica. Left untreated, it is fatal in most cases....

Im Focus: A “cosmic snake” reveals the structure of remote galaxies

The formation of stars in distant galaxies is still largely unexplored. For the first time, astron-omers at the University of Geneva have now been able to closely observe a star system six billion light-years away. In doing so, they are confirming earlier simulations made by the University of Zurich. One special effect is made possible by the multiple reflections of images that run through the cosmos like a snake.

Today, astronomers have a pretty accurate idea of how stars were formed in the recent cosmic past. But do these laws also apply to older galaxies? For around a...

Im Focus: Visual intelligence is not the same as IQ

Just because someone is smart and well-motivated doesn't mean he or she can learn the visual skills needed to excel at tasks like matching fingerprints, interpreting medical X-rays, keeping track of aircraft on radar displays or forensic face matching.

That is the implication of a new study which shows for the first time that there is a broad range of differences in people's visual ability and that these...

Im Focus: Novel Nano-CT device creates high-resolution 3D-X-rays of tiny velvet worm legs

Computer Tomography (CT) is a standard procedure in hospitals, but so far, the technology has not been suitable for imaging extremely small objects. In PNAS, a team from the Technical University of Munich (TUM) describes a Nano-CT device that creates three-dimensional x-ray images at resolutions up to 100 nanometers. The first test application: Together with colleagues from the University of Kassel and Helmholtz-Zentrum Geesthacht the researchers analyzed the locomotory system of a velvet worm.

During a CT analysis, the object under investigation is x-rayed and a detector measures the respective amount of radiation absorbed from various angles....

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Ecology Across Borders: International conference brings together 1,500 ecologists

15.11.2017 | Event News

Road into laboratory: Users discuss biaxial fatigue-testing for car and truck wheel

15.11.2017 | Event News

#Berlin5GWeek: The right network for Industry 4.0

30.10.2017 | Event News

 
Latest News

Underwater acoustic localization of marine mammals and vehicles

23.11.2017 | Information Technology

Enhancing the quantum sensing capabilities of diamond

23.11.2017 | Physics and Astronomy

Meadows beat out shrubs when it comes to storing carbon

23.11.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>