88 Uncovering the Pro-regenerative Cardiac Response to Bacterial Infection

Faculty Mentor: James A. Gagnon (School of Biological Sciences, University of Utah)

Humans lack robust mechanisms to resolve scarring caused by damage to the heart. After cardiac injury caused by events such as a myocardial infarction, humans form a non-contractile scar that chronically impairs heart function. In contrast, some species can regenerate damaged heart tissues allowing for full recovery after injury. Zebrafish, a species with robust cardiac regenerative capabilities, have been recognized as a crucial model to help us understand the regenerative response. Significant zebrafish regeneration research has been completed using various models of cardiac injury, but we still have not adequately explored the response to damage caused by a bacterial infection of the heart muscle (bacterial myocarditis). Bacterial myocarditis is known to cause fibrosis in non-regenerating hearts; however, we do not know whether regenerating hearts have the same response or whether they are able to resist damage. Injection of bacterial cell wall proteins has been used as a way to model systemic infections and, as is seen in bacterial myocarditis, injection has been found to cause cardiac fibrosis in mice. Interestingly, when zebrafish are injected with the same proteins, they turn on pro-regenerative pathways. I hypothesize that this ability to turn on this regenerative cascade protects zebrafish from significant fibrosis. To explore this hypothesis, I injected zebrafish and Japanese medaka, a similar teleost species that cannot regenerate its heart, with a bacteria lipoprotein and used various tools to understand the cardiac response. By continuing this work, I can begin to explore cardioprotective features that could also protect humans from scar formation.