Subterranean Fishes of the World

4315

2019

AIM 2019

65

Following myocardial infarction the human heart is unable to repair and forms a permanent scar that may later result in heart failure or recurring myocardial infarction. Unlike humans, the zebrafish is able to regenerate its heart following injury through significant myocardial proliferation. We have recently established the Astyanax mexicanus as a new and powerful model for cardiac regeneration, which allows us to compare fish-like regeneration with human-like scarring in a single species. In this model the surface fish regenerate their heart after injury while the fish from the Pachón cave cannot and, similar to humans, forms a permanent scar. Our RNAseq analysis has revealed strongly reduced activation of metabolic pathways after injury in the Pachón heart compared to surface fish, and these differences in cardiac metabolism could be central to why surface fish can regenerate cardiac tissue whilst the Pachón cannot. We have especially found that glucose metabolism related genes are highly upregulated in the surface fish heart but not in the Pachón after injury, and interestingly, expression of these genes are localised to the wound border where myocardial proliferation takes place – suggesting an importance of glucose metabolism in cell cycle and heart regeneration. Both the insulin and leptin/melanocortin pathways control the activation of cellular glucose metabolic pathways and are known to be mutated in cavefish. We have explored the expression of the insulin receptor and leptin genes following injury and are investigating the effect the P211L insulin receptor mutation on cardiac regeneration in the regenerating zebrafish. Investigating the metabolic response in the Astyanax mexicanus after injury, will help define the ideal metabolic environment for successful heart regeneration.

1

Astyanax Interrnational Meeting