Their findings appear in the journal Blood.
Blood clots are formed at the site of an injured blood vessel to prevent blood loss. Sometimes, however, blood clots completely clog an artery or vein and the surrounding tissues are damaged. The U.S. Centers for Disease Control and Prevention reports that annually, 300,000 to 600,000 Americans are afflicted with deep vein thrombosis or pulmonary embolism, a blocked lung artery that often results from thrombosis, and 60,000 to 100,000 people die each year as a result of these conditions.
There are two pathways that trigger blood clotting. The tissue factor pathway helps stop bleeding if a person is injured. If any of the proteins of this pathway are missing, a bleeding problem will develop. In contrast, the contact pathway is activated when blood comes into contact with some artificial substances. Although this pathway can cause pathological blood clots, humans who lack proteins in this pathway do not have bleeding problems. These two pathways eventually converge to form a common pathway.
In 2006, the researchers found that compounds called polyphosphates can, when released from cell fragments called platelets, activate the contact pathway, said University of Illinois biochemistry professor James H. Morrissey, who led that study and the new analysis.
Because the contact pathway is not essential for normal blood clotting after an injury, interrupting polyphosphate “wouldn’t have the bleeding side effects that touching anything downstream of it in the clotting cascade (would) have,” Morrissey said.
The researchers found a variety of positively charged molecules that can bind to the negatively charged polyphosphate molecule and inhibit its ability to induce blood clotting. By adding these compounds to human blood and plasma isolated from the body, Morrissey and his colleagues were able to measure their effectiveness in inhibiting polyphosphate’s pro-thrombotic and pro-inflammatory activities.
The researchers also tested these inhibitors in mice that were afflicted with venous and arterial thrombosis or inflammation, and found that these inhibitors prevented or reduced these negative effects.
“What this shows is that you could put really potent inhibitors of polyphosphate in and interrupt the clotting system by decreasing thrombotic risk, but probably not increasing (a person’s) bleeding risk,” Morrissey said. “This is the proof of principle that it works.”
Although the compounds identified would not, by themselves, be good drug candidates, Morrissey said, the new study offers clues for developing more suitable drugs to target polyphosphates.
“I think that the work going forward would be to identify compounds that would be better drug candidates,” he said.
The study team also included researchers from the Medical College of Wisconsin. The National Heart, Lung and Blood Institute at the National Institutes of Health supported this research.
Editor’s notes: To reach James H. Morrissey, call 217- 265-4036; email firstname.lastname@example.org.
The paper, “Inhibition of polyphosphate as a novel strategy for preventing thrombosis and inflammation,” is available online or from the U. of I. News Bureau.
Chelsey Coombs | University of Illinois
What the world's tiniest 'monster truck' reveals
23.08.2017 | American Chemical Society
Treating arthritis with algae
23.08.2017 | Empa - Eidgenössische Materialprüfungs- und Forschungsanstalt
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,...
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...
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...
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...
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...
16.08.2017 | Event News
04.08.2017 | Event News
26.07.2017 | Event News
23.08.2017 | Life Sciences
23.08.2017 | Life Sciences
23.08.2017 | Physics and Astronomy