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Stimulation of adenosine A2b receptors blocks apoptosis in the non-infarcted myocardium even when administered after the onset of infarction

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Abstract

Objective Chronic adenosine A2b receptor stimulation has been shown to prevent ventricular remodelling after myocardial infarction (MI). We hypothesized that this effect is due to the inhibition of cardiac myocyte apoptosis in the myocardium remote from the infarction. Methods Rats were subjected to MI by LAD ligation in situ. Some animals were pre-treated with the stable adenosine analogue 2-chloro-adenosine (CADO). After 24 h, pro- and anti-apoptotic signals (protein kinase C isoforms, p38, g proteins, Bcl-2/Bax ratio, Akt, Bad), and marker of apoptosis execution (caspase-3, TUNEL) were quantified in the remote myocardium. Results CADO prevented the occurrence of apoptosis in the remote myocardium of an infarcted heart. This effect occured not only when CADO was started before the onset of ischemia but also when it started 3 h after the infarction. The anti-apoptotic effect of CADO was blocked by simultaneous administration of the selective adenosine A2b receptor antagonist MRS1754 (1 mg/kg). The anti-apoptotic effect of CADO seems to be mediated by gαq and by the activation of survival kinases (Bad) and by inhibition of the pro-apoptotic PKC-δ/p38-MAPK-pathway. Conclusion Chronic adenosine A2b receptor stimulation blocks cardiac myocyte apoptosis in the remote myocardium even when started after the onset of infarction. This may explain the anti-remodelling-effect of the A2b receptor stimulation after infarction.

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Authors and Affiliations

  1. Department of Medicine and Cardiology, Dresden Heart Center, Dresden University of Technology, Fetscherstr. 76, 01307, Dresden, Germany

    Gregor Simonis, Stephan Wiedemann, Dirk Joachim, Christof Weinbrenner, Rainer Marquetant & Ruth H. Strasser

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  1. Gregor Simonis
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  2. Stephan Wiedemann
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  3. Dirk Joachim
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  4. Christof Weinbrenner
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  5. Rainer Marquetant
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  6. Ruth H. Strasser
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Correspondence to Gregor Simonis.

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Simonis, G., Wiedemann, S., Joachim, D. et al. Stimulation of adenosine A2b receptors blocks apoptosis in the non-infarcted myocardium even when administered after the onset of infarction. Mol Cell Biochem 328, 119–126 (2009). https://doi.org/10.1007/s11010-009-0081-x

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