Aims: Reactive oxygen species (ROS) activate multiple signaling
pathways involved in cardiac hypertrophy. Since HO-1 exerts potent antioxidant
effects, we hypothesized that this enzyme inhibits ROS-induced cardiomyocyte
hypertrophy. Methods: HL-1 cardiomyocytes were transduced with an
adenovirus constitutively expressing HO-1 (AdHO-1) to increase basal HO-1 expression
and then exposed to 200 μM hydrogen peroxide (H2O2).
Hypertrophy was measured using 3H-leucine incorporation, planar
morphometry and cell-size by forward-scatter flow-cytometry. The pro-oxidant effect
of H2O2 was assessed by redox sensitive fluorophores. Inducing
intracellular redox imbalance resulted in cardiomyocyte hypertrophy through
transactivation of nuclear factor kappa B (NF-κB). Results:
Pre-emptive HO-1 overexpression attenuated the redox imbalance and reduced
hypertrophic indices. This is the first time that HO-1 has directly been shown to
inhibit oxidant-induced cardiomyocyte hypertrophy by a NF-κB–dependent mechanism.
Conclusion: These results demonstrate that HO-1 inhibits
pro-oxidant induced cardiomyocyte hypertrophy and suggest that HO-1 may yield
therapeutic potential in treatment of
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