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This Article Full Text Full Text (PDF) All Versions of this Article: 293/3/H1833    most recent 00488.2007v1 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 Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (1) Citing Articles via Google Scholar Google Scholar Articles by Hu, C.-P. Articles by Mehta, J. L. Search for Related Content PubMed PubMed Citation Articles by Hu, C.-P. Articles by Mehta, J. L.

Blockade of hypoxia-reoxygenation-mediated collagen type I expression and MMP activity by overexpression of TGF-₁ delivered by AAV in mouse cardiomyocytes

¹Division of Cardiovascular Medicine, Gene Therapy Program, Department of Internal Medicine, University of Arkansas for Medical Sciences and Department of Veterans Affairs Medical Center, Little Rock, Arkansas; and ²Department of Pharmacology, School of Pharmaceutical Sciences, Central South University, Changsha, China

Submitted 24 April 2007 ; accepted in final form 17 June 2007

Transforming growth factor (TGF)-₁ is one of the most pleiotropic and multifunctional peptides known. While the cardioprotective effect of TGF-₁ during ischemia is well known, the specific role of TGF-₁ in altering the cardiac remodeling process remains unclear. This study was designed to examine the regulation of hypoxia-reoxygenation-mediated collagen type I expression and activity of matrix metalloproteinases (MMPs) by overexpression of TGF-₁ in cultured HL-1 mouse cardiomyocytes. TGF-₁ was overexpressed in cardiomyocytes by transfection with adeno-associated virus (AAV)/TGF-₁^Latent or with AAV/TGF-₁^ACT (active TGF-₁). Twenty-four hours of hypoxia followed by 3 h of reoxygenation (H-R) markedly enhanced (pro)collagen type I expression and activity of MMPs concomitant with an increase in reactive oxygen species (ROS) release and LOX-1 expression. Overexpression of TGF-₁ reduced these alterations induced by H-R. TGF-₁ overexpression also blocked H-R-mediated p38 and p44/42 MAPK activation. Transfection with AAV/TGF-₁^ACT was superior to that with AAV/TGF-₁^Latent. These data for the first time demonstrate that H-R induces signals for cardiac remodeling in cardiomyocytes and TGF-₁ can modulate, possibly via antioxidant mechanism, these signals. These findings contribute to further understanding of the role of TGF-₁ in the cardiac remodeling process.

transforming growth factor-₁; HL-1 adult murine cardiomyocytes; metalloproteinases

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