Grant: Operating Grant

Heart attacks and strokes are the number one cause of death and disability in Canada and world-wide. Most heart attacks and strokes are caused by blood clots that form on top of ruptured plaques inside heart or brain arteries. The consequences of such clots depend on how rapidly they form and how quickly they break down. Clots that form slowly and break down rapidly will produce few symptoms. In contrast, clots that do not break down can block the flow of blood in the arteries and trigger a heart attack or stroke. We are studying the factors that regulate clot formation and clot breakdown. There is a protein in the blood called histidine-rich glycoprotein (HRG). Blood levels of HRG are high, but we know very little about its function. We have evidence that HRG slows clotting and promotes clot break down. Based on these observations, we hypothesize that HRG is an important determinant of how fast clots form and subsequently break down at sites where plaques rupture. The purpose of this application is to test this hypothesis. We will explore the mechanisms by which HRG slows clotting and accelerates clot breakdown. This information is important because if HRG slows clot formation and accelerates clot breakdown, it may be useful for prevention or treatment of clots that form at sites where plaques rupture.