Navigation Links
UT Southwestern researchers uncover culprits in life-threatening clotting disorder
Date:12/3/2010

DALLAS Dec. 3, 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.


'/>"/>

Contact: Kristen Holland Shear
kristen.hollandshear@utsouthwestern.edu
214-648-3404
UT Southwestern Medical Center
Source:Eurekalert  

Related biology news :

1. Waste from gut bacteria helps host control weight, UT Southwestern researchers report
2. RSV may hide in the lungs, lead to asthma, UT Southwestern researchers report
3. UT Southwestern researcher awarded Gates Foundation grant for novel vaccine development
4. Deranged calcium signaling contributes to neurological disorder, UT Southwestern researchers find
5. UT Southwestern researchers identify gene linked to inherited form of fatal lung disease
6. UT Southwestern scientist honored among best in Texas research
7. Natural brain substance blocks weight gain in mice, UT Southwestern researchers discover
8. UT Southwestern researchers disrupt biochemical system involved in cancer, degenerative disease
9. UT Southwestern researchers identify molecule that helps the sleep-deprived to mentally rebound
10. Two UT Southwestern researchers awarded Sloan fellowships
11. Diabetics on high-fiber diets might need extra calcium, report UT Southwestern researchers
Post Your Comments:
*Name:
*Comment:
*Email:
Related Image:
UT Southwestern researchers uncover culprits in life-threatening clotting disorder
(Date:6/9/2016)... ISTANBUL , June 9, 2016  Perkotek an innovation leader in attendance control ... to seamlessly log work hours, for employers to make sure the right employees are ... Logo - http://photos.prnewswire.com/prnh/20160609/377486LOGO ... ... ...
(Date:6/2/2016)... 2016 The Department of Transport Management ... 44 million US Dollar project, for the , ... Personalization, Enrolment, and IT Infrastructure , to ... and implementation of Identity Management Solutions. Numerous renowned international vendors ... Decatur was selected for the most compliant and ...
(Date:5/24/2016)... 2016 Ampronix facilitates superior patient care by providing unparalleled technology to leaders ... is the latest premium product recently added to the range of products distributed by ... ... ... LCD Medical Display- Ampronix News ...
Breaking Biology News(10 mins):
(Date:6/23/2016)... ... June 23, 2016 , ... STACS DNA Inc., the sample tracking software company, ... Crime Laboratory, has joined STACS DNA as a Field Application Specialist. , “I ... President and COO of STACS DNA. “In further expanding our capacity as a scientific ...
(Date:6/23/2016)... June 23, 2016 Apellis Pharmaceuticals, Inc. ... clinical trials of its complement C3 inhibitor, APL-2. ... multiple ascending dose studies designed to assess the ... subcutaneous injection in healthy adult volunteers. ... as a single dose (ranging from 45 to ...
(Date:6/23/2016)... 2016 Andrew D ... http://doi.org/10.17925/OHR.2016.12.01.22 Published recently in ... from touchONCOLOGY, Andrew D Zelenetz , discusses ... care is placing an increasing burden on healthcare ... therapies. With the patents on many biologics expiring, ...
(Date:6/23/2016)... ... June 23, 2016 , ... ClinCapture, the only free validated ... will showcase its product’s latest features from June 26 to June 30, 2016 ... on Disrupting Clinical Trials in The Cloud during the conference. DIA (Drug ...
Breaking Biology Technology: