Anti-platelet agents are widely prescribed for prevention and management of cardiovascular disease (CVD). Even with the known efficacy of anti-platelet therapy, a substantial number of CVD events occur under active treatment, indicating the persistence of underlying pathophysiology. The central premise of this project is that specific biochemical pathways underlie inter-individual variation in efficacy of clopidogrel (Plavix) and aspirin and that metabolomic analyses in samples derived from studies of anti-platelet treatment will identify metabolic signatures that define drug response. The goal of this Bridging Project will be accomplished by using a variety of metabolomic platforms to identify and validate clinical and cellular metabolomic signatures of these anti-platelet agents. This will include both pretreatment metabolites that may serve as biomarkers for successful therapeutic response and metabolites that are themselves responsive to anti-platelet treatment and, as such, may highlight novel pathways involved in anti-platelet efficacy. This information will be used to identify metabolites, and their relevant genetic signatures that may be predictive of or contribute to inter-individual variation in anti-platelet mediated CVD risk reduction and their clinical application toward more effective personalized anti-platelet therapy.
|Alan Schuldiner||Amber Beitlelshees||Laura Yerges||Richard Horenstein|