Metabolic Reprogramming in Hypertrophic Cardiomyopathy

Lay Summary: This proposal is focused on defining if cardiac metabolism is altered in the early post-natal heart by disruptions in myofilament function in an effort to better understand the pathogenesis of hypertrophic cardiomyopathy (HCM). The proposed experimental plan outlines a comprehensive approach to determine what components of cardiac metabolism are altered in the setting of myofilament dysfunction during early post-natal cardiac development. In addition, we will utilize human derived cardiomyocytes to investigate if myofilament mutations cause hypertrophic cardiomyocyte growth through restriction of metabolic substrate utilization. The ultimate goal of this research is to identify novel pathways that can be targeted to prevent the development of hypertrophic cardiomyopathy in children genetically predisposed to this condition.