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Extracellular superoxide dismutase regulates cardiac function and fibrosis.

Publication ,  Journal Article
Kliment, CR; Suliman, HB; Tobolewski, JM; Reynolds, CM; Day, BJ; Zhu, X; McTiernan, CF; McGaffin, KR; Piantadosi, CA; Oury, TD
Published in: J Mol Cell Cardiol
November 2009

Extracellular superoxide dismutase (EC-SOD) is an antioxidant that protects the heart from ischemia and the lung from inflammation and fibrosis. The role of cardiac EC-SOD under normal conditions and injury remains unclear. Cardiac toxicity, a common side effect of doxorubicin, involves oxidative stress. We hypothesize that EC-SOD is critical for normal cardiac function and protects the heart from oxidant-induced fibrosis and loss of function. C57BL/6 and EC-SOD-null mice were treated with doxorubicin, 15 mg/kg (i.p.). After 15 days, echocardiography was used to assess cardiac function. Left ventricle (LV) tissue was used to assess fibrosis and inflammation by staining, Western blot, and hydroxyproline analysis. At baseline, EC-SOD-null mice have LV wall thinning and increases in LV end diastolic dimensions compared to wild-type mice but have normal cardiac function. After doxorubicin, EC-SOD-null mice have decreases in fractional shortening not apparent in WT mice. Lack of EC-SOD also leads to increases in myocardial apoptosis and significantly more LV fibrosis and inflammatory cell infiltration. Administration of the metalloporphyrin AEOL 10150 abrogates the loss of cardiac function, and potentially fibrosis, associated with doxorubicin treatment in both wild-type and EC-SOD KO mice. EC-SOD is critical for normal cardiac morphology and protects the heart from oxidant-induced fibrosis, apoptosis, and loss of function. The antioxidant metalloporphyrin AEOL 10150 effectively protects cardiac function from doxorubicin-induced oxidative stress in vivo. These findings identify targets for the use of antioxidant agents in oxidant-induced cardiac fibrosis.

Duke Scholars

Published In

J Mol Cell Cardiol

DOI

EISSN

1095-8584

Publication Date

November 2009

Volume

47

Issue

5

Start / End Page

730 / 742

Location

England

Related Subject Headings

  • Superoxide Dismutase
  • Random Allocation
  • Oxidative Stress
  • Myocardium
  • Mice, Knockout
  • Mice, Inbred C57BL
  • Mice
  • Immunohistochemistry
  • Hypertrophy, Left Ventricular
  • Heart
 

Citation

APA
Chicago
ICMJE
MLA
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Kliment, C. R., Suliman, H. B., Tobolewski, J. M., Reynolds, C. M., Day, B. J., Zhu, X., … Oury, T. D. (2009). Extracellular superoxide dismutase regulates cardiac function and fibrosis. J Mol Cell Cardiol, 47(5), 730–742. https://doi.org/10.1016/j.yjmcc.2009.08.010
Kliment, Corrine R., Hagir B. Suliman, Jacob M. Tobolewski, Crystal M. Reynolds, Brian J. Day, Xiaodong Zhu, Charles F. McTiernan, Kenneth R. McGaffin, Claude A. Piantadosi, and Tim D. Oury. “Extracellular superoxide dismutase regulates cardiac function and fibrosis.J Mol Cell Cardiol 47, no. 5 (November 2009): 730–42. https://doi.org/10.1016/j.yjmcc.2009.08.010.
Kliment CR, Suliman HB, Tobolewski JM, Reynolds CM, Day BJ, Zhu X, et al. Extracellular superoxide dismutase regulates cardiac function and fibrosis. J Mol Cell Cardiol. 2009 Nov;47(5):730–42.
Kliment, Corrine R., et al. “Extracellular superoxide dismutase regulates cardiac function and fibrosis.J Mol Cell Cardiol, vol. 47, no. 5, Nov. 2009, pp. 730–42. Pubmed, doi:10.1016/j.yjmcc.2009.08.010.
Kliment CR, Suliman HB, Tobolewski JM, Reynolds CM, Day BJ, Zhu X, McTiernan CF, McGaffin KR, Piantadosi CA, Oury TD. Extracellular superoxide dismutase regulates cardiac function and fibrosis. J Mol Cell Cardiol. 2009 Nov;47(5):730–742.
Journal cover image

Published In

J Mol Cell Cardiol

DOI

EISSN

1095-8584

Publication Date

November 2009

Volume

47

Issue

5

Start / End Page

730 / 742

Location

England

Related Subject Headings

  • Superoxide Dismutase
  • Random Allocation
  • Oxidative Stress
  • Myocardium
  • Mice, Knockout
  • Mice, Inbred C57BL
  • Mice
  • Immunohistochemistry
  • Hypertrophy, Left Ventricular
  • Heart