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Updated: Aug 15, 2026
Gene Transfer for Ischemic Heart Failure in a Preclinical Model
Published on: May 15, 2011
S100A1 gene therapy preserves in vivo cardiac function after myocardial infarction
Sven T Pleger1, Andrew Remppis, Beatrix Heidt
1Medizinische Universitätsklinik und Poliklinik III, Otto Meyerhof Zentrum, Universität zu Heidelberg, INF 350, 69115 Heidelberg, Germany.
Insights
Gene therapy using S100A1 improved heart function after myocardial infarction (MI) in rats. This treatment enhanced myocardial contractility and preserved cardiac function, offering a potential new therapy for heart attack patients.
Area of Science:
- Cardiology
- Molecular Biology
- Regenerative Medicine
Background:
- Myocardial infarction (MI) causes significant loss of heart muscle, leading to impaired left ventricular (LV) function and heart failure.
- S100A1 protein is known to positively regulate myocardial contractility.
- Effective treatments to preserve heart function post-MI are crucial.
Purpose of the Study:
- To investigate the therapeutic potential of S100A1 gene therapy for preserving heart function after MI.
- To evaluate the effects of S100A1 gene delivery on myocardial contractility and cardiac performance post-MI.
Main Methods:
- Rats induced with cryo-thermal MI received intracoronary delivery of adenoviral vectors carrying S100A1 or GFP (control).
- LV function was assessed one week post-MI using in vivo and ex vivo myocyte analyses.
- Cardiac hypertrophy and beta-adrenergic inotropic reserve were evaluated.
Main Results:
- S100A1 gene delivery significantly preserved global LV function one week after MI.
- S100A1 enhanced contractile parameters and calcium transients in isolated cardiomyocytes.
- Overexpression of S100A1 attenuated GRK2 upregulation and reduced cardiac hypertrophy.
Conclusions:
- Myocardial S100A1 gene therapy is a promising strategy to maintain contractile performance in the post-MI heart.
- S100A1 enhances contractility of viable myocardium and preserves cardiac function after ischemic injury.
- This approach offers a potential novel therapeutic avenue for managing heart attack consequences.
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 x 10(10) 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 Ca(2+) 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 beta-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.
