Researchers find promising new angle for drugs to prevent stroke and heart attack

August 30, 2013, University of North Carolina at Chapel Hill School of Medicine

Platelets, which allow blood to clot, are at the heart of numerous cardiovascular problems, including heart attacks and stroke. New research has uncovered a key platelet protein that could offer a new angle for developing drugs to prevent thrombosis, or dangerous blood clots, in patients who are at high risk such as those with atherosclerosis or a history of heart problems.

"I think we're at the start of an exciting journey of for a new class of antithrombotic therapies," said lead study author Stephen Holly, PhD, assistant professor of biochemistry and at the University of North Carolina School of Medicine. This work was performed in collaboration with senior authors Leslie Parise, PhD, at UNC and Benjamin Cravatt, PhD, at The Scripps Research Institute.

The study was published online August 29 ahead of print in the journal Chemistry & Biology and funded by grants from the American Heart Association and the National Institutes of Health.

In the human circulatory system, platelets are something of a double-edged sword. Without their clotting abilities, even a minor injury could result in potentially fatal bleeding. But during a or stroke, platelets form a clot that can potentially block blood flow through our veins and arteries, a dangerous condition called thrombosis, which can deprive tissues of oxygen and lead to death.

Several antithrombotic drugs are available, but some have been found to cause bleeding—a side effect that is particularly troublesome when these drugs are used to prevent thrombosis in people undergoing heart surgery. "There's still room for improvement, in terms of making an ideal drug that can block platelet function without initiating bleeding," said Dr. Holly.

Dr. Holly and his colleagues uncovered several potential drug targets using a screening technique that has never before been applied to the cardiovascular system. The technique, called activity-based protein profiling, has been used in cancer research and allows researchers to track the actual activities of proteins operating within a cell. The team first pre-screened human platelets to narrow the field of drug-like compounds, then generated an activity-based protein profile using one of these compounds to single out proteins that play a role in platelet activation.

The hunt was successful. "Using this technique, we discovered both novel inhibitors of platelet activation and a novel enzyme involved in platelet signaling," said Holly.

This new knowledge of platelets' natural "on-off" switches could be exploited to develop drugs that keep from forming pathological blood clots. As a next step, the researchers hope to investigate the proteins' roles in animal models before potentially pursuing clinical trials in humans.

Explore further: Researchers find key to blood-clotting process

Related Stories

Researchers find key to blood-clotting process

June 26, 2013
Researchers, including Professor Alastair Poole and Dr Matthew Harper from the University of Bristol's School of Physiology and Pharmacology, have uncovered a key process in understanding how blood clots form that could help ...

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 ...

New type of blood stem cell could help solve platelet shortage

August 13, 2013
Scientists funded by the Medical Research Council (MRC) have identified a new type of bone marrow stem cell in mice that is primed to produce large numbers of vital blood-clotting platelets. The breakthrough may eventually ...

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

October 29, 2012
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 ...

Clingy platelets suggest potential treatment strategy for rheumatoid arthritis

August 29, 2013
No one likes clingy people, but "clingy" blood platelets may offer hope for millions of people with rheumatoid arthritis. According to new research findings published in The Journal of Leukocyte Biology, a sub population ...

1-year results of ADAPT-DES trial published in The Lancet

July 26, 2013
Patients who receive a drug-eluting stent (DES) and demonstrate high platelet reactivity on clopidogrel are more likely to have blood clots form on the stent and to suffer a heart attack; however, these patients are less ...

Recommended for you

More surprises about blood development—and a possible lead for making lymphocytes

January 22, 2018
Hematopoietic stem cells (HSCs) have long been regarded as the granddaddy of all blood cells. After we are born, these multipotent cells give rise to all our cell lineages: lymphoid, myeloid and erythroid cells. Hematologists ...

How metal scaffolds enhance the bone healing process

January 22, 2018
A new study shows how mechanically optimized constructs known as titanium-mesh scaffolds can optimize bone regeneration. The induction of bone regeneration is of importance when treating large bone defects. As demonstrated ...

Bioengineered soft microfibers improve T-cell production

January 18, 2018
T cells play a key role in the body's immune response against pathogens. As a new class of therapeutic approaches, T cells are being harnessed to fight cancer, promising more precise, longer-lasting mitigation than traditional, ...

Weight flux alters molecular profile, study finds

January 17, 2018
The human body undergoes dramatic changes during even short periods of weight gain and loss, according to a study led by researchers at the Stanford University School of Medicine.

Secrets of longevity protein revealed in new study

January 17, 2018
Named after the Greek goddess who spun the thread of life, Klotho proteins play an important role in the regulation of longevity and metabolism. In a recent Yale-led study, researchers revealed the three-dimensional structure ...

The HLF gene protects blood stem cells by maintaining them in a resting state

January 17, 2018
The HLF gene is necessary for maintaining blood stem cells in a resting state, which is crucial for ensuring normal blood production. This has been shown by a new research study from Lund University in Sweden published in ...

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.