Researchers at the University of Rochester Medical Center recently discovered a new “signpost” molecule that may lead to a breakthrough in understanding how platelets, tiny cells that are important for blood clotting, get switched on after heart attack and stroke. This knowledge could eventually yield new specialized drugs that could turn platelets off and prevent excessive clotting in these circumstances, which would reduce damage to heart and brain tissue.
In normal conditions, platelets are tiny “plate-like” cells that slide along our vessel walls. If they reach a tear in a vessel – as would happen if you got a bruise or a cut - they “turn on”, change shape, and become very sticky. The platelets clump onto the breaks in the vessel, as well as onto one another. This effectively patches the tear and stops the bleeding. In this instance, platelets can save your life. However, when platelets turn on after a heart attack, they can clog blood vessels and block blood and oxygen flow to the heart, brain, and lungs, causing tissue damage at these sites.
Herein lies the heart of the issue: how do you prevent platelets from being turned on after heart attack or stroke without impairing their normal function. “It’s a delicate balance of inhibiting when you need to, but not inhibiting too much,” says Scott Cameron, M.D., Ph.D., Cardiology Fellow in the Aab Cardiovascular Research Institute at the University of Rochester Medical Center and author of the study.
Current platelet inhibitor drugs do not strike this balance. Most of these drugs carry a risk of excess bleeding and many are simply ineffective for a portion of heart attack or stroke patients. This often leaves both patients and doctors baffled, including Cameron. “I have to tell my patients that they got the right medicine and I’m not sure why it did not work, but they need another surgery. That, for me, is not very satisfying.”
Craig Morrell, D.V.M., Ph.D., Associate Professor of Medicine in the Aab Cardiovascular Research Institute at the University of Rochester Medical Center and co-author of the study, says the shortcomings of current drugs can be traced to the fact that all of the previous research in this field studied how platelets work in healthy conditions. According to Morrell, “the field keeps studying over and over how platelets turn on in normal conditions, but what’s really important is how platelets act after someone’s had a heart attack. Our study is important because it shows that platelet function is different after you’ve had a heart attack.”
Morrell and Cameron believe their study, published in the journal Circulation, may be the key to developing more specific platelet inhibitors that would prevent bleeding complications. They found that platelets can be turned on when they experience a lack of oxygen – as occurs in a heart attack or stroke. The “signpost” molecule they identified senses the increase in free radicals caused by the lack of oxygen and keeps the platelets turned on – worsening the blockage of blood flow.
While this discovery is potentially a great advance, Morrell and Cameron’s work is far from done. They plan to thoroughly study this new way to turn platelets on in hopes of finding an optimal drug target to turn them off after heart attack or stroke. They hope their research will lead to development of a drug that can tip the balance toward helping patients without the risks carried by current drugs.
To download the full study, click here
The University of Rochester Medical Center is home to approximately 3,000 individuals who conduct research on everything from cancer and heart disease to Parkinson’s, pandemic influenza, and autism. Spread across many centers, institutes, and labs, our scientists have developed therapies that have improved human health locally, in the region, and across the globe. To learn more, visit http://www.urmc.rochester.edu/research.