Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

UT Southwestern researchers uncover culprits in life-threatening clotting disorder

06.12.2010
Thanks to findings by UT Southwestern Medical Center researchers, individuals with a potentially life-threatening condition predisposing them to blood clots, or thrombosis, might someday receive therapy to prevent the condition.

The findings, available online and in a future issue of The Journal of Clinical Investigation, offer new clues into the mechanisms underlying antiphospholipid syndrome (APS).

"Patients with APS have circulating antibodies that cause exaggerated thrombosis. The longstanding mystery has been how these antibodies initiate the clotting," said Dr. Philip Shaul, professor of pediatrics and senior co-author of the study.

For the study, the researchers first examined the direct actions of APS antibodies on cultured endothelial cells, which line the inside of blood vessels.

They discovered that the thrombosis-inducing antibodies recognize a protein called Beta2-Glycoprotein I on the endothelial cell surface that then interacts with a second protein, apolipoprotein E receptor 2 (apoER2). ApoER2 ultimately inactivates the enzyme that produces the antithrombotic molecule nitric oxide. The decrease in nitric oxide causes both white blood cells and platelets to bind to the endothelium, initiating the thrombosis.

Dr. Shaul said the findings are quite promising because they identify the series of molecular events responsible for the exaggerated thrombosis.

The study also found that in contrast to normal mice, mice genetically engineered to lack apoER2 are completely protected from developing thrombosis when they are given APS antibodies collected from individuals with the syndrome.

"Patients with thrombosis often require lifelong anti-coagulation therapy," he said. "The problem with this approach is that the anti-coagulation can be ineffective, and there are multiple potential serious complications related to bleeding. It makes much more sense to develop new therapies that target the underlying disease mechanism."

Dr. Chieko Mineo, assistant professor of pediatrics and senior co-author of the study, said the findings are particularly important for pregnant women with APS because they are at high risk of miscarriage and preterm birth.

"Even if a woman with APS does carry to term, the infant is often smaller than normal and can suffer from multiple complications," Dr. Mineo said. "Our ongoing studies indicate that the mechanisms we have identified that provoke thrombosis are also operative in APS during pregnancy to adversely affect the health of both the mother and the fetus."

The next step, Dr. Shaul said, is to test in the mouse models three novel therapeutic interventions that are based on the new understanding of APS.

"If they prevent thrombosis or pregnancy complications in the mouse models, clinical trials would of course follow," Dr. Shaul said.

Other UT Southwestern researchers involved in the study include lead author Dr. Sangeetha Ramesh, former graduate research assistant in pediatrics; Dr. Cristina Tarango, former postdoctoral fellow in pediatric hematology/oncology; Ivan Yuhanna, senior research associate in pediatrics; Dr. Joachim Herz, professor of molecular genetics and neuroscience; Dr. Philip Thorpe, professor of pharmacology; and Dr. Gail Thomas, former associate professor of internal medicine. Researchers from the University of Rochester School of Medicine and Dentistry, Weill Cornell Medical College and University Medical Center Utrecht in the Netherlands also participated.

The study was supported by the National Institutes of Health, the Alliance for Lupus Research, The Lowe Foundation, the Crystal Charity Ball Center for Pediatric Critical Care Research, and the Robert L. Moore Endowment from Children's Medical Center Foundation.

Visit http://www.utsouthwestern.org/pediatrics to learn more about clinical services in pediatrics at UT Southwestern.

This news release is available on our World Wide Web home page at http://www.utsouthwestern.edu/home/news/index.html

To automatically receive news releases from UT Southwestern via e-mail, subscribe at www.utsouthwestern.edu/receivenews

Kristen Holland Shear | EurekAlert!
Further information:
http://www.utsouthwestern.edu

More articles from Life Sciences:

nachricht Repairing damaged hearts with self-healing heart cells
22.08.2017 | National University Health System

nachricht Biochemical 'fingerprints' reveal diabetes progression
22.08.2017 | Umea University

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Fizzy soda water could be key to clean manufacture of flat wonder material: Graphene

Whether you call it effervescent, fizzy, or sparkling, carbonated water is making a comeback as a beverage. Aside from quenching thirst, researchers at the University of Illinois at Urbana-Champaign have discovered a new use for these "bubbly" concoctions that will have major impact on the manufacturer of the world's thinnest, flattest, and one most useful materials -- graphene.

As graphene's popularity grows as an advanced "wonder" material, the speed and quality at which it can be manufactured will be paramount. With that in mind,...

Im Focus: Exotic quantum states made from light: Physicists create optical “wells” for a super-photon

Physicists at the University of Bonn have managed to create optical hollows and more complex patterns into which the light of a Bose-Einstein condensate flows. The creation of such highly low-loss structures for light is a prerequisite for complex light circuits, such as for quantum information processing for a new generation of computers. The researchers are now presenting their results in the journal Nature Photonics.

Light particles (photons) occur as tiny, indivisible portions. Many thousands of these light portions can be merged to form a single super-photon if they are...

Im Focus: Circular RNA linked to brain function

For the first time, scientists have shown that circular RNA is linked to brain function. When a RNA molecule called Cdr1as was deleted from the genome of mice, the animals had problems filtering out unnecessary information – like patients suffering from neuropsychiatric disorders.

While hundreds of circular RNAs (circRNAs) are abundant in mammalian brains, one big question has remained unanswered: What are they actually good for? In the...

Im Focus: RAVAN CubeSat measures Earth's outgoing energy

An experimental small satellite has successfully collected and delivered data on a key measurement for predicting changes in Earth's climate.

The Radiometer Assessment using Vertically Aligned Nanotubes (RAVAN) CubeSat was launched into low-Earth orbit on Nov. 11, 2016, in order to test new...

Im Focus: Scientists shine new light on the “other high temperature superconductor”

A study led by scientists of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science in Hamburg presents evidence of the coexistence of superconductivity and “charge-density-waves” in compounds of the poorly-studied family of bismuthates. This observation opens up new perspectives for a deeper understanding of the phenomenon of high-temperature superconductivity, a topic which is at the core of condensed matter research since more than 30 years. The paper by Nicoletti et al has been published in the PNAS.

Since the beginning of the 20th century, superconductivity had been observed in some metals at temperatures only a few degrees above the absolute zero (minus...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Call for Papers – ICNFT 2018, 5th International Conference on New Forming Technology

16.08.2017 | Event News

Sustainability is the business model of tomorrow

04.08.2017 | Event News

Clash of Realities 2017: Registration now open. International Conference at TH Köln

26.07.2017 | Event News

 
Latest News

Cholesterol-lowering drugs may fight infectious disease

22.08.2017 | Health and Medicine

Meter-sized single-crystal graphene growth becomes possible

22.08.2017 | Materials Sciences

Repairing damaged hearts with self-healing heart cells

22.08.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>