Heart attack gene, MRP-14, triggers blood clot formation

April 4, 2014

Currently, options are limited for preventing heart attacks. However, the day may come when treatments target the “heart attack gene,” myeloid related protein-14 (MRP-14, also known as S100A9), and eliminate its ability to produce heart attack-inducing blood clots—the process of thrombosis. Scientists at Case Western Reserve School of Medicine and University Hospitals Case Medical Center have studied humans and mice and discovered how MRP-14 generates dangerous clots that could trigger heart attack or stroke, and what happens when MRP-14 is manipulated. Their study, which appears online in The Journal for Clinical Investigation, describes a previously unrecognized platelet-dependent pathway of thrombosis.

“We have now closed the loop of our original finding that MRP-14 is a heart attack gene,” says lead author Daniel I. Simon, MD. “We describe a new pathway that shows clotting platelets have MRP-14 inside them, that platelets secrete MRP-14, and that MRP-14 binds to a platelet receptor called CD36 to activate platelets.”

This translational research has moved back and forth from the cardiac catheterization laboratory, investigating patients presenting with heart attack, to the basic research lab, probing mechanisms of disease. The clinical portion of this research yielded a stunning element—blood clots extracted from an occluded heart artery loaded with MRP-14-containing platelets. In detailed studies using MRP-14-deficient mice, investigators discovered MRP-14 in action. One key finding is that, while MRP-14 is required for pathologic blood clotting, it does not appear to be involved in the natural, primary hemostasis response to prevent bleeding.

“This research may provide a new target to develop more effective and safer anti-thrombotic agents,” Simon says. Current anti-clotting drugs are subject to significant bleeding risk, which is associated with increased mortality. Read the article.

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