S100A1 gene therapy preserves in vivo cardiac function after myocardial infarction

Sven T. Pleger, Andrew Remppis, Beatrix Heidt, Mirko Völkers, J. Kurt Chuprun, Matthew Kuhn, Rui Hai Zhou, Erhe Gao, Gabor Szabo, Dieter Weichenhan, Oliver J. Müller, Andrea D. Eckhart, Hugo A. Katus, Walter J. Koch, Patrick Most

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70 Citations (Scopus)

Abstract

Myocardial infarction (MI) represents an enormous clinical challenge as loss of myocardium due to ischemic injury is associated with compromised left ventricular (LV) function often leading to acute cardiac decompensation or chronic heart failure. S100A1 was recently identified as a positive inotropic regulator of myocardial contractility in vitro and in vivo. Here, we explore the strategy of myocardial S100A1 gene therapy either at the time of, or 2 h after, MI to preserve global heart function. Rats underwent cryothermia-induced MI and in vivo intracoronary delivery of adenoviral transgenes (4 × 1010 pfu). Animals received saline (MI), the S100A1 adenovirus (MI/AdS100A1), a control adenovirus (MI/AdGFP), or a sham operation. S100A1 gene delivery preserved global in vivo LV function 1 week after MI. Preservation of LV function was due mainly to S100A1-mediated gain of contractility of the remaining, viable myocardium since contractile parameters and Ca2+ transients of isolated MI/AdS100A1 myocytes were significantly enhanced compared to myocytes isolated from both MI/AdGFP and sham groups. Moreover, S100A1 gene therapy preserved the cardiac β-adrenergic inotropic reserve, which was associated with the attenuation of GRK2 up-regulation. Also, S100A1 overexpression reduced cardiac hypertrophy 1 week post-MI. Overall, our data indicate that S100A1 gene therapy provides a potential novel treatment strategy to maintain contractile performance of the post-MI heart.

Original languageEnglish
Pages (from-to)1120-1129
Number of pages10
JournalMolecular Therapy
Volume12
Issue number6
DOIs
Publication statusPublished - Dec 1 2005

Keywords

  • Contractile function
  • Gene therapy
  • Myocardial infarction
  • S100A1

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics
  • Pharmacology
  • Drug Discovery

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  • Cite this

    Pleger, S. T., Remppis, A., Heidt, B., Völkers, M., Chuprun, J. K., Kuhn, M., Zhou, R. H., Gao, E., Szabo, G., Weichenhan, D., Müller, O. J., Eckhart, A. D., Katus, H. A., Koch, W. J., & Most, P. (2005). S100A1 gene therapy preserves in vivo cardiac function after myocardial infarction. Molecular Therapy, 12(6), 1120-1129. https://doi.org/10.1016/j.ymthe.2005.08.002