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This Article Full Text Full Text (PDF) All Versions of this Article: 297/4/H1504    most recent 00194.2009v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Li, L. Articles by Minatoguchi, S. PubMed PubMed Citation Articles by Li, L. Articles by Minatoguchi, S.

Postinfarction gene therapy with adenoviral vector expressing decorin mitigates cardiac remodeling and dysfunction

¹Division of Cardiology, Gifu University Graduate School of Medicine, Gifu; ²Department of Gene Therapy and Regenerative Medicine, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima; ³Division of Gene Therapy and Regenerative Medicine, Cognitive and Molecular Research Institute of Brain Diseases, Kurume University, Kurume; and ⁴Department of Food Science, Kyoto Women's University, Kyoto, Japan

Submitted March 2, 2009 ; accepted in final form August 12, 2009

The small leucine-rich proteoglycan decorin is a natural inhibitor of transforming growth factor-β (TGF-β) and exerts antifibrotic effects in heart and to stimulate skeletal muscle regeneration. We investigated decorin's chronic effects on postinfarction cardiac remodeling and dysfunction. Myocardial infarction (MI) was induced in mice by left coronary artery ligation. An adenoviral vector encoding human decorin (Ad. CAG-decorin) was then injected into the hindlimbs on day 3 post-MI (control, Ad.CAG-LacZ). Four weeks post-MI, the decorin-treated mice showed significant mitigation of the left ventricular dilatation and dysfunction seen in control mice. Although infarct size did not differ between the two groups, the infarcted wall thickness was greater and the segmental length of the infarct was smaller in decorin-treated mice. In addition, cellular components, including myofibroblasts and blood vessels, were more abundant within the infarcted area in decorin-treated mice, and fibrosis was significantly reduced in both the infarcted and noninfarcted areas of the left ventricular wall. Ten days post-MI, there was greater cell proliferation and less apoptosis among granulation tissue cells in the infarcted areas of decorin-treated mice. The treatment, however, did not affect proliferation and apoptosis of salvaged cardiomyocytes. Although decorin gene therapy did not affect TGF-β1 expression in the infarcted heart, it inhibited Smad2/3 activation (downstream mediators of TGF-β signaling). In summary, postinfarction decorin gene therapy mitigated cardiac remodeling and dysfunction by altering infarct tissue noncardiomyocyte dynamics and preventing cardiac fibrosis, accompanying inhibition of Smad2/3 activation.

heart failure; myocardial infarction; transforming growth factor-β