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Heme oxygenase-1 (HO-1) inhibits postmyocardial infarct remodeling and restores ventricular function.

Publication ,  Journal Article
Liu, X; Pachori, AS; Ward, CA; Davis, JP; Gnecchi, M; Kong, D; Zhang, L; Murduck, J; Yet, S-F; Perrella, MA; Pratt, RE; Dzau, VJ; Melo, LG
Published in: FASEB J
February 2006

We reported previously that predelivery of the anti-oxidant gene heme oxygenase-1 (HO-1) to the heart by adeno associated virus (AAV) markedly reduces injury after acute myocardial infarction (MI). However, the effect of HO-1 gene delivery on postinfarction recovery has not been investigated. In the current study, we assessed the effect of HO-1 gene delivery on post-MI left ventricle (LV) remodeling and function using echocardiographic imaging and histomorphometric approaches. Two groups of Sprague-Dawley rats were injected with 4 x 10(11) particles of AAV-LacZ (control) or AAV-hHO-1 in the LV wall. Eight wk after gene transfer, the animals were subjected to 30 min of ischemia by ligation of left anterior descending artery (LAD) followed by reperfusion. Echocardiographic measurements were obtained in a blinded fashion prior and at 1.5 and 3 months after I/R. Ejection fraction (EF) was reduced by 13% and 40% in the HO-1 and LacZ groups, respectively at 1.5 months after MI. Three months after MI, EF recovered fully in the HO-1, but only partially in the LacZ-treated animals. Post-MI LV dimensions were markedly increased and the anterior wall was markedly thinned in the LacZ-treated animals compared with the HO-1-treated animals. Significant myocardial scarring and fibrosis were observed in the LacZ-group in association with elevated levels of interstitial collagen I and III and MMP-2 activity. Post-MI myofibroblast accumulation was reduced in the HO-1-treated animals, and retroviral overexpression of HO-1 reduced proliferation of isolated cardiac fibroblasts. Our data indicate that rAAV-HO-1 gene transfer markedly reduces fibrosis and ventricular remodeling and restores LV function and chamber dimensions after myocardial infarction.

Duke Scholars

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Published In

FASEB J

DOI

EISSN

1530-6860

Publication Date

February 2006

Volume

20

Issue

2

Start / End Page

207 / 216

Location

United States

Related Subject Headings

  • Ventricular Remodeling
  • Ventricular Function
  • Rats, Sprague-Dawley
  • Rats
  • Myocardium
  • Myocardial Reperfusion Injury
  • Myocardial Infarction
  • Male
  • Humans
  • Heme Oxygenase-1
 

Citation

APA
Chicago
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MLA
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Liu, X., Pachori, A. S., Ward, C. A., Davis, J. P., Gnecchi, M., Kong, D., … Melo, L. G. (2006). Heme oxygenase-1 (HO-1) inhibits postmyocardial infarct remodeling and restores ventricular function. FASEB J, 20(2), 207–216. https://doi.org/10.1096/fj.05-4435com
Liu, Xiaoli, Alok S. Pachori, Christopher A. Ward, J Paul Davis, Massimiliano Gnecchi, Deling Kong, Lunan Zhang, et al. “Heme oxygenase-1 (HO-1) inhibits postmyocardial infarct remodeling and restores ventricular function.FASEB J 20, no. 2 (February 2006): 207–16. https://doi.org/10.1096/fj.05-4435com.
Liu X, Pachori AS, Ward CA, Davis JP, Gnecchi M, Kong D, et al. Heme oxygenase-1 (HO-1) inhibits postmyocardial infarct remodeling and restores ventricular function. FASEB J. 2006 Feb;20(2):207–16.
Liu, Xiaoli, et al. “Heme oxygenase-1 (HO-1) inhibits postmyocardial infarct remodeling and restores ventricular function.FASEB J, vol. 20, no. 2, Feb. 2006, pp. 207–16. Pubmed, doi:10.1096/fj.05-4435com.
Liu X, Pachori AS, Ward CA, Davis JP, Gnecchi M, Kong D, Zhang L, Murduck J, Yet S-F, Perrella MA, Pratt RE, Dzau VJ, Melo LG. Heme oxygenase-1 (HO-1) inhibits postmyocardial infarct remodeling and restores ventricular function. FASEB J. 2006 Feb;20(2):207–216.

Published In

FASEB J

DOI

EISSN

1530-6860

Publication Date

February 2006

Volume

20

Issue

2

Start / End Page

207 / 216

Location

United States

Related Subject Headings

  • Ventricular Remodeling
  • Ventricular Function
  • Rats, Sprague-Dawley
  • Rats
  • Myocardium
  • Myocardial Reperfusion Injury
  • Myocardial Infarction
  • Male
  • Humans
  • Heme Oxygenase-1