Booth Id:
BMED038T
Category:
Biomedical and Health Sciences
Year:
2019
Finalist Names:
Agyeman-Mensah, Boatemaa (School: Breck School)
Gunderson, Rachel (School: Breck School)
Abstract:
Heart disease is the number one killer worldwide, resulting in 800,000 American deaths annually.
Scarring of the heart, due to cardiomyocyte death during myocardial infarctions, compromises
the muscles’ capability to pump blood in a normal rhythm. Cardiomyocytes turnover at a rate of
less than 1% per year making natural proliferation of cardiomyocytes insufficient when it comes
to regenerating the human heart. Although there are currently no approved treatments to
enhance the low proliferative capabilities of cardiomyocytes, a number of genes are known to
affect cardiomyocyte proliferation.
Preliminary work on the gene Asxl2 reported improved proliferation and de novo cardiomyocyte
formation in a knockout mouse model. As a first step to studying the underlying mechanism of
Asxl2 mediated inhibition of cardiomyocyte proliferation, we attempted to validate these
published results in an Asxl2 knockout mouse model. Tissue samples from wild type and
knockout mice were stained on sites positively possessing EdU, a synthetic thymidine analog
which marked replicating cells. Immunohistochemistry with cardiomyocyte marking antibodies
was used to identify cardiac muscle cells. Images were taken on a fluorescent microscope and
quantified to compare cardiomyocyte size, the number of EdU+ cardiomyocytes, and the number
of EdU+ non-cardiomyocytes between the knockout and wild type models. The average number
of proliferative cardiomyocytes was higher in Asxl2 knockout mice, although this did not reach
statistical significance. Further examination regarding the mechanism of Asxl2-dependent gene
and chromatin regulation in relation to cardiomyocyte proliferation is warranted in hopes of
developing a therapeutic treatment for cardiovascular disease.