Targeting a clot protein to prevent heart attacks

Identifying the origin of plasma FXIII-A and defining the roles of cellular FXIII-A

Blood clots prevent excess bleeding from cuts to the skin, but they can also be dangerous. For example, heart attacks, many strokes, and deep vein thrombosis all occur when clots form inside a blood vessel in the body. The main component of blood clots is a protein called fibrin, which forms long chains. These chains are strengthened by connecting bridges made of a protein called FXIII-A. This is useful to toughen scabs on the skin, but may make it more difficult to remove a blood clot if it forms in the blood vessels. Reducing FXIII-A activity has been proposed as a way of reducing heart attack risk. But it’s complicated, because research shows that FXIII-A has a second role in repairing and strengthening tissues, which may be beneficial for the heart. Some FXIII-A is free in the bloodstream, while some is packaged up in cells, including cells from the immune system. Now, Professor Richard Pease at the University of Leeds will try to determine whether this difference in the location of FXIII-A is important for the difference between forming blood clots and carrying out repair roles. If so, it might be possible to selectively increase the activity of FXIII-A in the location that encourages repair, while reducing the activity of FXIII-A that toughens clots. This could open up a new avenue for design of drugs to prevent or treat heart attacks and other clot-caused health problems.