PR001748 (Project)

Description:We propose the use of targeted metabolomics to define the metabolic and molecular pathways altered in 2 mouse models (R92W-TnT and R403Q-MHC) of hypertrophic cardiomyopathy (HCM) that span the spectrum of human disease (heart failure and sudden death), with the goal of identifying treatment targets. Parallel targeted metabolomics studies will be performed in heart tissue and plasma at rest and following inotrope stimulation. Since energy compromise is expected to be most marked when the heart is subject to increased workload, as is the case during high-intensity exercise or inotropic stimulation, we propose metabolomics studies in heart tissue and plasma, at rest and following inotrope stimulation. We anticipate that the results of these studies will allow us to move forward with further investigations into specific metabolites of interest as biomarkers, to be tested in HCM patients in future studies.