artery; platelets loaded with
MRP-14 shown in yellow.
Journal of Clinical Investigation
Investigators say they’ve discovered how myeloid related protein-14 (MRP-14) generates thrombi that can trigger myocardial infarction (MI) or stroke.
Previous research showed that MRP-14 is elevated in platelets from patients who present with acute MI.
In the current study, researchers found that platelet-derived MRP-14 directly regulates thrombosis, and CD36 is required for this process.
The team therefore believes we could target this platelet-dependent pathway to treat atherothrombotic disorders.
“This is exciting because we have now closed the loop of our original finding that MRP-14 is a heart attack gene,” said investigator Daniel I. Simon, MD, of the University Hospitals Harrington Heart & Vascular Institute in Cleveland, Ohio.
“We now describe a whole 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.”
Dr Simon and his colleagues recounted these findings in The Journal of Clinical Investigation.
The research alternated between the cardiac catheterization lab (where researchers were investigating MI patients) to the basic research lab (where the investigators were probing mechanisms of disease).
The clinical portion of this research yielded thrombi—extracted from an occluded heart artery—that were loaded with platelets containing MRP-14.
“It is remarkable that this abundant platelet protein promoting thrombosis could have gone undetected until now,” Dr Simon said.
In experiments on MRP-14-deficient mice, he and his colleagues observed MRP-14 in action. One key finding was that, while MRP-14 is required for pathologic thrombosis, it does not appear to be involved in the natural, primary hemostasis response to prevent bleeding.
“The practical significance of this research is that it may provide a new target to develop more effective and safer antithrombotic agents,” Dr Simon said.
“If we could develop an agent that affects pathologic clotting and not hemostasis, that would be a home run. You would have a safer medication to treat pathologic clotting in heart attack and stroke.”
