Scientists' discovery of blood clotting mechanism could lead to new antithrombotic drugs
For the first time, researchers have identified the specific mechanism of von Willebrand Factor (vWF) -- an essential blood clotting protein -- that enables it to bind to platelets and initiate clotting
2021-04-28
(Press-News.org) Under normal, healthy circulatory conditions, the von Willebrand Factor (vWF) keeps to itself. The large and mysterious glycoprotein moves through the blood, balled up tightly, its reaction sites unexposed. But when significant bleeding occurs, it springs into action, initiating the clotting process.
When it works properly, vWF helps stop bleeding and saves lives. However, according to the Centers for Disease Control and Prevention (CDC), about 60,000 to 100,000 Americans die each year from thrombosis, a disorder characterized by too much clotting. Blood clots can trigger a stroke or heart attack.
According to X. Frank Zhang, associate professor in the Department of Bioengineering at Lehigh University, only one drug has been FDA-approved to target vWF and treat thrombosis, or excessive blood clotting disorders, Caplacizumab. It works by binding to vWF and blocking it from binding to platelets. However, no one has understood the specific mechanism behind how it accomplishes this.
Until now, for the first time, Zhang and his colleagues from Emory University School of Medicine and the University of Nottingham have identified the specific structural element of vWF that allows it to bind with platelets and initiate clotting. The team says that the specific unit, which they call the discontinuous autoinhibitory module, or AIM, is a prime site for new drug development. The work is described in an article published last week in Nature Communications, "Activation of von Willebrand factor via mechanical unfolding of its discontinuous autoinhibitory module."
"The AIM module allows the vWF molecule to remain non-reactive in normal circulating blood, and activates the vWF instantly upon bleeding," says Zhang. "In our research, we identified that Caplacizumab works by binding the AIM region of vWF and enhancing the force threshold to mechanically remove vWF's autoinhibitory structures, opening up a new avenue to the development of antithrombotic drugs targeting the AIM structures."
An essential feature of vWF is that it remains non-reactive towards platelets most of the time in circulation, says Zhang. However, at bleeding sites, vWF can be activated almost instantly to achieve platelet adhesion and blood clot formation. In this research, the team identified a structural element, AIM, located around the portion of vWF, called the A1 domain, that is responsible for binding platelets.
"In normal circulating blood," explains Zhang "the AIM wraps around the A1 and prevents the A1 from interacting with platelets. However, at the binding site, the blood flow pattern change leads to enough hydrodynamic force to stretch the AIM and pull it away from the A1, allowing the A1 to grab platelets to the bleeding site."
Zhang, who has been studying vWF for years, specializes in single-molecule force spectroscopy and mechanosensing, or how cells respond to mechanical stimuli. He uses a specialized tool called optical tweezers, which utilizes a focused laser beam to apply force to objects as small as a single molecule.
"Optical tweezers can grab tiny objects," Zhang explains. "We can grab the vWF and at the same time we apply force to see how the protein changes shape, to see how the proteins are activated when there's a mechanical perturbation or a mechanical force."
Zhang says that before conducting the study, the team suspected that they would find an autoinhibitory module, given previous research by co-corresponding author Renhao Li at Emory.
"However, we did not expect this inhibitory module to play such an important role in vWF," says Zhang. "It not only controls the vWF activation for platelet interaction, but plays a role in triggering some types of von Willebrand disease, a hereditary bleeding disease affecting one percent of the human population."
INFORMATION:
ELSE PRESS RELEASES FROM THIS DATE:
2021-04-28
Today at the Microbiology Society's Annual Conference, Yang Liu, researcher at Hong Kong Polytechnic University, will discuss a new technique to trap and recover microplastics.
The method uses bacterial biofilms, a sticky substance created by micro-organisms, to trap microplastic particles. The biofilm is then processed and dispersed, releasing the microplastic particles for processing and recycling.
Liu and colleagues used the bacterium Pseudomonas aeruginosa to capture microplastics in a bioreactor. This species of bacteria is found in all environments and has previously been shown to colonise microplastics in the environment.
P. aeruginosa biofilms ...
2021-04-28
Research shows that children who experience puberty earlier than their peers are more likely to begin drinking alcohol at a young age and early alcohol exposure is also known to be related to alcohol dependence later in life. Specifically, adolescents who mature early are two to three times more likely to drink than other youth. In addition, early maturing girls are two to three times more likely to drink until intoxication and three times as likely to have an alcohol use disorder. A new study examined why early developing 14-year-old adolescents are more likely to drink alcohol compared to those whose pubertal development is on-time or late. The findings show these adolescents are more likely to have ...
2021-04-28
Frequent use of exemptions may undermine public health protections of oil and gas setback policies, according to a new study led by researchers at the research institute PSE Healthy Energy, Harvard University, and Nicholas Institute for Environmental Solutions at Duke University. The study, published April 28, 2021 in Energy Policy, is the first to assess the effectiveness of distance-based setback regulations for unconventional natural gas development (UNGD) or "fracking."
"Setback regulations are commonly employed to protect public health, so we wanted to test if they're effective in practice," said lead author Drew Michanowicz, DrPH, ...
2021-04-28
In a new nationwide poll, the GeneSight® Mental Health Monitor found that 83% of people with depression agree that life would be easier if others could understand their depression. Yet, most people who have not experienced depression may not be able to understand the challenges, including its treatment.
"Depression is one of the most misunderstood disorders. When people misinterpret patients with depression as 'lazy' or 'dramatic,' they are vastly underestimating and misunderstanding the debilitating symptoms of major depressive disorder," said Mark Pollack, M.D., chief medical officer for the GeneSight test at Myriad ...
2021-04-28
UNIVERSITY PARK, Pa. -- Parents of teens who went through puberty early may be more lenient when it comes to letting them consume alcohol, according to a new Penn State study. But the researchers said that even if adolescents appear more mature, drinking alcohol is still not safe for them.
Rebecca Bucci, a PhD candidate in criminology at Penn State, said the study -- published today (April 28) in Child Development -- aimed to discover why adolescents who go through puberty early are more likely than their peers to drink alcohol.
"A surprising proportion of parents in our study allowed their early-developing children to drink alcohol at the age of 14 -- in fact, ...
2021-04-28
CLEVELAND, Ohio (April 28, 2021)--Hot flashes are a hallmark of the menopause transition. Yet, they don't strike with the same frequency or severity for all women. A new study suggests that some of the same genetic factors that affect a woman's reproductive life cycle may also help predict her likelihood of having bothersome hot flashes. Study results are published online today in Menopause, the journal of The North American Menopause Society (NAMS).
Despite multiple studies on the subject, questions still remain as to why some women are more affected than others by hot flashes and night sweats during the menopause transition. Genetics may be one reason, ...
2021-04-28
Whether you hanker for a hard hit of caffeine or favour the frothiness of a milky cappuccino, your regular coffee order could be telling you more about your cardio health than you think.
In a world first study of 390,435 people, University of South Australia researchers found causal genetic evidence that cardio health - as reflected in blood pressure and heart rate - influences coffee consumption.
Conducted in partnership with the SAHMRI, the team found that people with high blood pressure, angina, and arrythmia were more likely to drink less coffee, decaffeinated coffee or avoid coffee altogether compared to those without such symptoms, and that this was based on genetics.
Lead researcher ...
2021-04-28
CHARGE syndrome is a rare genetic disorder affecting about 1 in 10,000 newborns. It can lead to neurological and behavioural disorders for which no treatment is currently available. Dr. Kessen Patten and his team, from the Institut national de la recherche scientifique (INRS) have just discovered a compound that could alleviate these symptoms. The results of their research were published in the journal EMBO Reports.
Understanding Neurological Disorders
First described in 1979, CHARGE syndrome is caused by mutations in the CHD7 gene and is associated with neurodevelopmental disorders such as intellectual disability, attention deficit disorder with or without hyperactivity, seizures and autism spectrum disorder. Dr. Patten's research team studied the ...
2021-04-28
Washington State University researchers have shown the fundamental mechanisms that allow tiny pieces of plastic bags and foam packaging at the nanoscale to move through the environment.
The researchers found that a silica surface such as sand has little effect on slowing down the movement of the plastics, but that natural organic matter resulting from decomposition of plant and animal remains can either temporarily or permanently trap the nanoscale plastic particles, depending on the type of plastics.
The work, published in the journal Water Research, could help researchers develop better ways to filter out and clean up pervasive plastics from the environment. The researchers include Indranil Chowdhury, assistant professor in WSU's Department of Civil and Environmental ...
2021-04-28
Over recent decades, community-based environmental monitoring (often called "citizen science") has exploded in popularity, aided both by smartphones and rapid gains in computing power that make the analysis of large data sets far easier.
Publishing in BioScience, handling editors Rick Bonney, of Cornell University, Finn Danielsen, of the Nordic Foundation for Development and Ecology, and colleagues share a special section that highlights numerous community-based monitoring programs currently underway. They also describe the potential for such efforts to advance the scientific enterprise well into the future and make recommendations for best practices and future directions.
In an article ...
LAST 30 PRESS RELEASES:
[Press-News.org] Scientists' discovery of blood clotting mechanism could lead to new antithrombotic drugs
For the first time, researchers have identified the specific mechanism of von Willebrand Factor (vWF) -- an essential blood clotting protein -- that enables it to bind to platelets and initiate clotting
