Ischemic heart disease is a leading cause of death worldwide. However, heart transplantation is risky, plus the number of donors does not cover the demand of patients, and alternative treatments are inefficient. Given that adult mammalian hearts display insufficient regeneration capability to allow complete myocardial recovery, a promising treatment after infarction could be the identification of molecules unblocking cardiac self-healing/regeneration. In that sense, zebrafish displays life-long ability to regenerate its heart after damage. Interestingly, the same genetic programs promoting cardiomyocyte dedifferentiation and proliferation after injury in zebrafish are present, albeit dormant, in the adult mammalian heart. This makes zebrafish a powerful model to unravel key molecular pathways that might induce heart regeneration in humans, if activated. Here, we propose the development of ZeNewCardio: a high-throughput preclinical platform using the zebrafish model to find suitable treatments for heart regeneration after ischemia. The project aims are: 1) to implement cardiac injury models in zebrafish; 2) to use these models to identify genes involved in heart regeneration, with a focus on genes enabling cardiomyocyte dedifferentiation/proliferation; 3) to use the gathered knowledge to discover novel cardiac pro-regeneration drug therapies applicable to humans. Our genetic and analysis tools will speed-up the process of target validation of novel gene regulators of regeneration, based on the stimulation of endogenous regenerative responses, and the discovery of new drug therapies to treat or protect ischemic hearts.
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