Hypoxia is a fetal stressor that leads to the production of endothelin-1 (ET-1). Previous
work has shown that ET-1 treatment leads to the premature terminal differentiation of fetal cardiomyocytes.
However, the precise mechanism is unknown. We tested the hypothesis that the fetal cardiomyocyte
proteome will be greatly altered due to ET-1-treatment, which reveals a potential molecular
mechanism of ET-1-induced terminal differentiation. Over a thousand proteins were detected in
the fetal cardiomyocytes and among them 75 proteins were significantly altered due to ET-1 treatment.
Using IPA pathway analysis, the merged network depicted several key proteins that appeared to
be involved in regulating proliferation, including: EED, UBC, ERK1/2, MAPK, Akt, and EGFR.
EED protein, which is associated with regulating proliferation via epigenetic mechanisms, is of particular
interest. Herein we propose a model of the molecular mechanism by which ET-1 induced cardiomyocyte
terminal differentiation occurs.
Keywords: Cardiomyocyte, Endothelin-1, EED, Fetal, Heart, Proliferation, Proteome.
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