S100A1 Gene Therapy Preserves in Vivo Cardiac Function after Myocardial Infarction.
Sven T. Pleger1,2, Andrew Remppis1, Beatrix Heidt1, Mirko Völkers1, J. Kurt Chuprun2, Matthew Kuhn2, Rui-Hai Zhou2, Erhe Gao2, Gabor Szabo3, Dieter Weichenhan1, Oliver J. Müller1, Andrea D. Eckhart2, Hugo A. Katus1, Walter J. Koch2 and Patrick Most1,2
1Medizinische Universitätsklinik und Poliklinik III, Otto Meyerhof Zentrum, Universität zu Heidelberg, INF 350, 69115 Heidelberg, Germany
2Center for Translational Medicine, Jefferson Medical College, 1025 Walnut Street, Philadelphia, PA 19107, USA
3Chirurgische Klinik der Universität Heidelberg, Abteilung für Herzchirurgie, INF 110, 69120 Heidelberg, Germany
MOLECULAR THERAPY. Vol. 12, No. 6, December 2005.





Brief Summary:
  • > 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 Badrenergic 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.