PAR4 Mediates an Elevated Risk for Thrombosis in Blacks Relative to Whites (425.1)

Coronary heart disease (CHD) is the leading cause of mortality in the US amongst all races. CHD disproportionality burdens blacks relative to whites and even after adjusting for other demographic parameters, blacks have a two-fold increase in incidence of CHD and a decrease in long-term survival. Occlusive thrombus formation is the underlying cause of mortality associated with CHD. Due to the importance of platelets in CHD and formation of occlusive thrombi, the response of platelets from blacks and whites to thrombin and its protease-activated receptors (PAR1 and PAR4) was characterized. Platelets isolated from blacks and whites differentially responded to PAR4 but not PAR1. Specifically, platelets from blacks were hyperaggregable to low and intermediate doses of PAR4-activating peptide (PAR4-AP) compared to platelets from whites. The mechanism responsible for the racial difference in PAR4 mediated platelet reactivity however is still unknown. We hypothesize that changes in expression or activity of prot...