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Investigation of the cellular mechanisms that promote cardiac regeneration in the MRL/MpJ+/+ mouse

Reference	BB/C509458/1
Principal Investigator / Supervisor	Professor Gavin Brooks
Co-Investigators / Co-Supervisors	Professor Katrina Bicknell, Professor Michael Marber
Institution	University of Reading
Department	Animal and Microbial Sciences
Funding type	Research
Value (£)	274,885
Status	Completed
Type	Research Grant
Start date	11/04/2005
End date	10/11/2008
Duration	43 months

Abstract

In most mammals, the loss of the proliferative capacity of the vast majority of adult heart muscle cells (cardiomyocytes) during cardiac development leads to the inability of the heart to regenerate itself following injury, such as following myocardial infarct. In the absence of cardiomyocyte cell division, an inflexible scar replaces the necrotic tissue of the infarct and thus, overall cardiac function is impaired. The cellular mechanisms that limit cardiac regeneration in mammals have yet to be fully elucidated. Recently, it has been shown that the MRL mouse strain displays a unique capacity for cardiac regeneration, the extent to which is not observed in other mouse strains. Complete regeneration without scarring is observed in MRL mouse hearts following cardiac injury, a phenomenon that previously has only been reported in non-mammalian species, e.g. zebrafish and newts. Hence, comparative analysis between the MRL mouse strain and non-regenerative mouse strains with similar genetic backgrounds offers a unique opportunity to dissect the molecular and cellular mechanisms that prevent efficient myocardial repair of the mammalian heart following injury. Differences in the proliferative potential and response to ischemia in regenerating MRL and non-regenerating control mouse strains will be examined. For the first time, the regenerative response to left ventricular injury in MRL mice will be investigated. Using proteomics-based strategies, the molecular and cellular differences between in the in vivo responses to injury in regenerating MRL and non-regenerating control mouse strains will be explored. The proteins shown to be differentially expressed in regenerating MRL mouse hearts compared to C57BL/6 controls will be investigated further using adenoviral-mediated gene transfer and RNA interference studies. It is anticipated that the programme of work described in this application will identify proteins that permit or prevent cardiac regeneration in the adult mammalian heart. An increased understanding of the cellular processes that govern myocardial repair and regeneration in the mammalian heart would prove invaluable in the design of therapeutic strategies aimed at inducing myocyte cell division and repair in the infarcted heart.

Summary

unavailable

Committee	Closed Committee - Genes & Developmental Biology (GDB)
Research Topics	Regenerative Biology
Research Priority	X – Research Priority information not available
Research Initiative	X - not in an Initiative
Funding Scheme	X – not Funded via a specific Funding Scheme

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