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

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.

Related Stories

Researchers find key to blood-clotting process

Jun 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 ...

Blood cell breakthrough could help treat heart disease

Apr 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 ...

Recommended for you

The impact of bacteria in our guts

2 hours ago

The word metabolism gets tossed around a lot, but it means much more than whether you can go back to the buffet for seconds without worrying about your waistline. In fact, metabolism is the set of biochemical ...

Stem cell therapies hold promise, but obstacles remain

3 hours ago

(Medical Xpress)—In an article appearing online today in the journal Science, a group of researchers, including University of Rochester neurologist Steve Goldman, M.D., Ph.D., review the potential and ch ...

New hope in fight against muscular dystrophy

4 hours ago

Research at Stockholm's KTH Royal Institute of Technology offers hope to those who suffer from Duchenne muscular dystrophy, an incurable, debilitating disease that cuts young lives short.

Biologists reprogram skin cells to mimic rare disease

22 hours ago

Johns Hopkins stem cell biologists have found a way to reprogram a patient's skin cells into cells that mimic and display many biological features of a rare genetic disorder called familial dysautonomia. ...

User comments