Exploring the Function of Heart Regeneration in Survival of Anoxia in Embryos of the Annual Killifish Austrofundulus limnaeus

Cardiovascular disease is the leading cause of death in the world, half of which is caused by myocardial infarction (MI) or heart attack. Most of the damage resulting from MI is due to oxygen deprivation that leads to cell death. The resulting cardiac scarring due to MI is chronic in humans and is not yet treatable; the only method of restoration is heart transplantation. Other organisms, such as fishes, show great cardiac regenerative capacity. The annual killifish, Austrofundulus limnaeus, can survive for months without oxygen at certain developmental stages. Examining gene expression responses during anoxic exposure and recovery in killifish embryos may offer a robust cardiovascular model for heart regeneration and offer insights into gene pathways that aid in cardioregenerative processes. My research will focus on the expression and activity of GATA4, a cofactor known to strongly correlate with heart regeneration in mice, during anoxic exposure and recovery periods in killifish embryos. Weighted correlation network analysis will also be used to find genes whose expression correlates with GATA4 to discover gene pathways which may aid in anoxia tolerance. Additionally, a small molecule inhibitor of GATA4 (3i-1000) will be used to elaborate on the importance of GATA4 in anoxic tolerance.