Heme oxygenase-1 inhibits pro-oxidant induced hypertrophy in HL-1 cardiomyocytes

Exp Biol Med (Maywood). 2009 May;234(5):582-94. doi: 10.3181/0810-RM-312. Epub 2009 Feb 25.


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 microM 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-kappaB).

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-kappaB-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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoviridae
  • Animals
  • Cardiomegaly / enzymology*
  • Cardiomegaly / genetics
  • Cardiomegaly / therapy
  • Cell Line
  • Heme Oxygenase (Decyclizing) / genetics
  • Heme Oxygenase (Decyclizing) / metabolism*
  • Hydrogen Peroxide / pharmacology*
  • Myocytes, Cardiac / enzymology*
  • NF-kappa B / metabolism
  • Oxidants / pharmacology*
  • Oxidation-Reduction
  • Rats
  • Transduction, Genetic


  • NF-kappa B
  • Oxidants
  • Hydrogen Peroxide
  • Heme Oxygenase (Decyclizing)
  • Hmox1 protein, rat