Research reveals new aspect of platelet behavior in heart attacks: Clots can sense blood flow

October 29, 2012
The microfluidic device the research team used to observe the flow-dependent clotting behavior.

The disease atherosclerosis involves the build up of fatty tissue within arterial walls, creating unstable structures known as plaques. These plaques grow until they burst, rupturing the wall and causing the formation of a blood clot within the artery. These clots also grow until they block blood flow; in the case of the coronary artery, this can cause a heart attack.

New research from the University of Pennsylvania has shown that clots forming under arterial-flow conditions have an unexpected ability to sense the surrounding blood moving over it.  If the flow stops, the clot senses the decrease in flow and this triggers a contraction similar to that of a muscle. The contraction squeezes out water, making the clot denser.

Better understanding of the clotting dynamics that occur in , as opposed to the dynamics at play in closing a wound, could lead to more effective drugs for prevention. 

The research was conducted by graduate student Ryan Muthard and Scott Diamond, professor and chair of the Department of Chemical and Biomolecular Engineering in the School of Engineering and Applied Science. 

Their work was published in the journal Arteriosclerosis, and , which is published by the .

"Researchers have known for decades that blood sitting in a test tube will clot and then contract to squeeze out water," Muthard said.  "Yet clots observed inside injured mouse blood vessels don't display much contractile activity.  We never knew how to reconcile these two studies, until an unexpected observation in the lab."

Using a specially designed microfluidic device, the researchers pulsed fluorescent dye across a clot to investigate how well it blocked bleeding. When they stopped the flow in order to adjust a valve to deliver the dye, the researchers were startled to see that a massive contraction was triggered in the clot. If they delivered the dye without stopping flow, there was no change in the clot properties.

"We think this may be one of the fundamental differences between clots formed inside blood vessels that cause thrombosis and clots formed when blood slowly pools around a leaking blood vessel during a bleeding event," Diamond said. "The flow sensing alters the clot mechanics." 

To investigate this alteration, the researchers used an intracellular fluorescent dye that binds to calcium. They found that when the flow stops, the platelets' calcium levels increase and they become activated. By adding drugs that block ADP and thromboxane, chemicals involved in the clotting process, the researchers were able to prevent this platelet calcium mobilization and stop the contraction.   

Millions of patients already take drugs that target these chemical pathways: P2Y12 inhibitors, such as Plavix, block ADP signaling in platelets, and aspirin blocks platelets' synthesis of thromboxane. This discovery suggests that these drugs may be interfering with contractile mechanisms that are triggered when ADP and thromboxane become elevated, such as when the flow around the clot decreases or stops.  Beyond slowing the growth of clots, these anti-platelet drugs may also be altering the mechanics of the clot by preventing contraction. 

"It is an example of 'quorum sensing' by the platelets in the clots," Diamond said. "The platelets are sensing each other and the prevailing environment. This causes them to release ADP and thromboxane, but it is rapidly diluted away by the surrounding

"However, when the flow over the clot decreases or stops, the ADP and thromboxane levels rapidly build up, and this drives platelet ," Diamond said.

Explore further: Scientists develop large-scale simulation of human blood

More information: atvb.ahajournals.org/content/e … 75-adab-e9be5b4ba202

Related Stories

Scientists develop large-scale simulation of human blood

May 1, 2012
(Medical Xpress) -- Having a virtual copy of a patient’s blood in a computer would be a boon to researchers and doctors. They could examine a simulated heart attack caused by blood clotting in a diseased coronary artery ...

Blood cell breakthrough could help treat heart disease

April 27, 2012
(Phys.org) -- Scientists at the University of Reading have made a groundbreaking discovery into the way blood clots are formed, potentially leading to the development of new drugs to treat one of the world's biggest killer ...

Researchers discover that JAM-A protein keeps blood clots in check

May 3, 2012
those disc-shaped cells circulating in your blood -- rush to the scene, clumping together to plug the leak.

Gelatin-based nanoparticle treatment may be a more effective clot buster

November 14, 2011
A targeted, nanoparticle gelatin-based clot-busting treatment dissolved significantly more blood clots than a currently used drug in an animal study of acute coronary syndrome presented at the American Heart Association's ...

Recommended for you

Engineered protein treatment found to reduce obesity in mice, rats and primates

October 19, 2017
(Medical Xpress)—A team of researchers with pharmaceutical company Amgen Inc. report that an engineered version of a protein naturally found in the body caused test mice, rats and cynomolgus monkeys to lose weight. In their ...

New procedure enables cultivation of human brain sections in the petri dish

October 19, 2017
Researchers at the University of Tübingen have become the first to keep human brain tissue alive outside the body for several weeks. The researchers, headed by Dr. Niklas Schwarz, Dr. Henner Koch and Dr. Thomas Wuttke at ...

Cancer drug found to offer promising results in treating sepsis in test mice

October 19, 2017
(Medical Xpress)—A combined team of researchers from China and the U.S. has found that a drug commonly used to treat lung cancer in humans offers a degree of protection against sepsis in test mice. In their paper published ...

Tracing cell death pathway points to drug targets for brain damage, kidney injury, asthma

October 19, 2017
University of Pittsburgh scientists are unlocking the complexities of a recently discovered cell death process that plays a key role in health and disease, and new findings link their discovery to asthma, kidney injury and ...

Study reveals key molecular link in major cell growth pathway

October 19, 2017
A team of scientists led by Whitehead Institute has uncovered a surprising molecular link that connects how cells regulate growth with how they sense and make available the nutrients required for growth. Their work, which ...

Inflammation trains the skin to heal faster

October 18, 2017
Scars may fade, but the skin remembers. New research from The Rockefeller University reveals that wounds or other harmful, inflammation-provoking experiences impart long-lasting memories to stem cells residing in the skin, ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.