Archana Boopathy

Heart failure is the leading cause of death worldwide. According to the 2011 update of the American Heart Association, one American will die of a coronary event every minute. While heart transplantation is the most viable treatment option, the limited availability of donor hearts has necessitated the search for treatment alternatives such as the use of adult stem cells for cardiac repair and regeneration. Following myocardial infarction (MI), the inflammatory cardiac microenvironment, limited survival of stem and progenitor cells, myocardial scarring and fibrosis affect cardiac regeneration. This proposal will examine adult stem cell based approaches for cardiac regeneration. As levels of H2O2 are elevated after MI, the effect of H2O2 on mesenchymal stem cell differentiation will be studied. The effect of activation of Notch1 signaling in cardiac progenitor cells using a self-assembling peptide scaffold containing the peptide ligand JAG1 will be determined in vitro and the functional consequences in a rat model of MI will be investigated. These approaches will address the central hypothesis that modulation of stem cells using micro environmental cues can aid in cardiac regeneration and improve functional outcome following myocardial infarction.