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Mechanisms of apoptosis after ischemia and reperfusion: Role of the renin-angiotensin system

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Abstract

Background: Apoptosis plays a key role in the pathogenesis of cardiac diseases. We examined the influence of the renin-angiotensin system (RAS) on different regulators of apoptosis using an isolated hemoperfused working porcine heart model of acute ischemia (2 h), followed by reperfusion (4 h). Methods and Results: 23 porcine hearts were randomized to 5 groups: hemoperfused non-infarcted hearts (C), infarcted hearts (MI: R. circumflexus), infarcted hearts treated with quinaprilat (Q), infarcted hearts treated with angiotensin-I (Ang I), and infarcted hearts treated with angiotensin-I and quinaprilat (QA). Fas, Bax, bcl-2 and p53 proteins were increased in MI hearts and further elevated by Ang I. Quinaprilat reduced Bax and p53. Bcl-2 was elevated in Q and reduced in QA. An early upregulation of caspase-3 gene and protein expression was detected in MI and Ang I hearts compared to C. Q reduced caspase-3 gene expression, but had no effect on caspase-3 and Fas protein. Conclusions: These data suggest that the RAS plays a pivotal role in cardiac apoptosis which is the early and predominant form of death in myocardial infarction. Ischemia/reperfusion induces programmed cell death via extrinsic and intrinsic pathways. Early treatment with quinaprilat attenuated cardiomyocyte apoptosis.

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Abbreviations

Ang::

angiotensin

LV::

left ventricle

Q::

quinaprilat

MI::

infarct group.

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Author information

Authors and Affiliations

  1. Institute of Clinical Pharmacology and Toxicology, Charité-University Medicine Berlin, Benjamin Franklin Campus, Berlin, Germany

    P. Kossmehl, E. Kurth, S. Faramarzi, B. Habighorst, M. Wehland, R. Kreutz, J. Grosse, M. Paul & D. Grimm

  2. Institute of Anatomy, Charité-University Medicine Berlin, Benjamin Franklin Campus, Berlin, Germany

    M. Shakibaei

  3. Institute of Anatomy, Ludwig-Maximilians-University, Munich, Germany

    M. Shakibaei

  4. Department of Trauma and Reconstructive Surgery, Charité-University Medicine Berlin, Benjamin Franklin Campus, Berlin, Germany

    M. Infanger

  5. Department of Pharmacology, Erasmus Medical Centre, Rotterdam, The Netherlands

    A. H. J. Danser

  6. Institute of Clinical Pharmacology and Toxicology, Charité-University Medical School, CBF Garystr. 5, D-14195, Berlin, Germany

    D. Grimm

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  1. P. Kossmehl
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  2. E. Kurth
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  3. S. Faramarzi
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  5. M. Shakibaei
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  6. M. Wehland
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  7. R. Kreutz
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  8. M. Infanger
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  9. A. H. J. Danser
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  10. J. Grosse
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  11. M. Paul
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  12. D. Grimm
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Corresponding author

Correspondence to D. Grimm.

Additional information

P. Kossmehl and E. Kurth contributed equally.

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Kossmehl, P., Kurth, E., Faramarzi, S. et al. Mechanisms of apoptosis after ischemia and reperfusion: Role of the renin-angiotensin system. Apoptosis 11, 347–358 (2006). https://doi.org/10.1007/s10495-006-4350-9

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  • DOI: https://doi.org/10.1007/s10495-006-4350-9

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