yocardial infarction and stroke typically result from an occlusive platelet thrombus formed at the site of atherosclerotic plaques.
There is reproducible variation in platelet reactivity among different individuals ? a variation that likely contributes to thrombosis
risk. The Platelet RNA And eXpression-1 (PRAX1) study was designed to identify novel genes and miRNAs responsible for inter-
individual variation in platelet reactivity. We assessed platelet aggregation in 70 black and 84 white healthy subjects and profiled
miRNA and mRNA from highly purified blood platelets. The richness of these data provided unique opportunities to establish miRNA-
mRNA-physiology relationships that led to a number of novel and unexpected results. This includes the discovery of racial differences
in PAR4-mediated platelet activation and a genetic regulatory module in which racial differences in expression of miRNAs located in
the DLK1-DIO3 locus and their target mRNAs account for this racial difference in platelet function. Compared to whites, blacks have
a 2-fold increase in the incidence of CHD and a lower long-term survival. In addition, it is unknown whether the racial difference in
platelet reactivity impacts the benefits and risks of anti-platelet therapies. Because novel inhibitors of PAR1 and 4 are currently in
clinical development, it is critical to know whether dosing of such agents should be adjusted by race to maximize benefit and avoid
toxicity. Lastly, since PAR4 is expressed in tissues other than platelets, it is possible that these expression differences have consequences
for non-thrombotic diseases known to show racial differences.
Leonard C. Edelstein has completed his Ph.D. from Rutgers University and postdoctoral studies from Harvard Medical School. He is a Research
Assistant Professor in the Cardeza Foundation for Hematologic Research at Thomas Jefferson University. He has published 14 papers in reputed
journals in the field of gene expression.
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