Tools to study the epicardium's response during cardiac regeneration

2013-04-29Cardiovascular disease is the number one cause of mortality worldwide and when not fatal contributes to chronic morbidity and decreased lifespan. Treating cardiovascular disease is a medical priority and suitable treatments continue to elude the medical field. Increasing interest in adult tissue regeneration as a solution to the medical burden of adulthood disease, including cardiac pathologies, has occurred with the identification of adult stem cells and organ regeneration in vertebrate animals. I used vertebrate animals as tools for studying cardiac regeneration. We utilized the adult mouse with a coronary artery ligation to evaluate the effects of Fgf10 on cardiac repair after ischemic injury. We also developed a neonatal mouse injury model to evaluate Fgf10 on the endogenous regeneration process, specifically the effect on epicardial cells. Additionally we developed a primary zebrafish epicardial cell culture for in vitro assays on the epicardial cells during regeneration. These tools allowed us to study the effect of a gene’s expression, in this study Fgf10, on the heart after injury and in endogenous repair/ regeneration processes. It was determined that Fgf10 does not have significant improvement on the cardiac regeneration process since it did not reduce the fibrosis in the heart in adult or neonatal mice, but does have an effect on epicardial cell proliferation during the injury response. Overexpression of Fgf10 increased proliferation of the Wilm’s tumor -1 expressing cells after injury, resulting in increased epicardial cells in the injury site. The significance of influencing epicardial cells during injury corroborates prior publications indicating epicardium response to injury is beneficial to repair and makes it an ideal target for therapies. This study identified Fgf10 as candidate growth factor in improving the response of the epicardium to cardiac injury and suggests further evaluation is warranted