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Cardiomyocyte regeneration in non-ischaemic cardiomyopathy

Lookup NU author(s): Dr Andrew Owens, Dr Gavin Richardson

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Abstract

Although cardiac regeneration has been demonstrated in the mammalian heart following ischemic injury, little is known regarding cardiomyocyte regeneration in non-ischemic cardiomyopathies, which represent 30% of cases of heart failure and includes patients with muscular dystrophy. We hypothesised that the mammalian heart can respond to chronic cardiomyocyte loss with the regeneration of new cardiomyocytes and tested this by examining cardiomyocyte regeneration during dilated cardiomyopathy in the Mdx mouse model of Duchenne muscular dystrophy. Adult mice were administered BrdU daily for one week and hearts were analysed using an optimised flow cytometry based protocol to detect the small subpopulation of BrdU labelled (regenerated) cardiomyocytes. Cells showing BrdU incorporation due to polyploidy were excluded from the analysis. We observed that the proportion of regenerated cardiomyocytes was significantly higher in the Mdx mouse compared to age matched controls (2.21%±0.93 versus 0.43%±0.37; p<0.005). To confirm our findings we next sought to visualise this population of regenerated cardiomyocytes using a histological approach. Confocal microscopy with Z-stack analysis identified a rare population of BrdU labelled, mono-nuclear cardiomyocytes in the hearts of mdx mice. This study is the first demonstration of increased cardiomyocyte regeneration in a non-ischemic model of cardiomyopathy. If the mammalian heart can respond to chronic cardiomyocyte loss with increased regeneration of new cardiomyocytes, this suggests that enhancing this endogenous regenerative potential is a valid therapeutic strategy for the treatment of non-ischaemic heart failure.


Publication metadata

Author(s): Owens WA, Richardson GD

Publication type: Conference Proceedings (inc. Abstract)

Publication status: Published

Conference Name: Weinstein Cardiovascular Conference

Year of Conference: 2014

Pages: 191


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