Grant: Project Grant

Platelets are circulating blood particles normally responsible for stopping bleeding by forming blood clots (platelet aggregates). In conditions such as heart attack and stroke blood clots form inappropriately in sick (atherosclerotic) blood vessels. Recently, we have discovered that two types of platelets exists. One type of platelet generates the signaling molecule nitric oxide and the other type of platelet does not generate this signaling molecule. Nitric oxide is well known to inhibit platelet clot formation, and we have found that platelets that do not generate nitric oxide initiate clot formation, while platelets that do generate nitric oxide limit clot formation. Additionally, we have preliminary data that suggests that the two platelet subtypes may respond differently to (anti-platelet) drugs that are used to prevent heart attack or stroke. Hence, the purpose of our studies are 1) to characterize the responses of NO-based platelet subtypes to commonly used anti-platelet drugs, and 2) to investigate whether heart attack patients have altered ratios of one type of platelet to another and to study how this altered ratio effects the patient's response to anti-platelet therapy. By the end of our studies we expect to have established that the two platelet subtypes differ in their response to antiplatelet drugs and that heart attack patients with an elevated ratio of non-NO-producing to NO-producing platelets may not fully respond to current anti-platelet therapy. These basic and translational studies of platelet biology have the potential to significantly impact the health of Canadians by better predicting risk and extent of clot formation. Lastly, these studies have the potential to inform personal anti-platelet therapy, and to potentially inform the future development of more effective anti-platelet drugs.