Secretome of apoptotic peripheral blood cells APOSEC confers cytoprotection to cardiomyocytes and inhibits tissue remodelling after acute myocardial infarction: a preclinical studyReport as inadecuate




Secretome of apoptotic peripheral blood cells APOSEC confers cytoprotection to cardiomyocytes and inhibits tissue remodelling after acute myocardial infarction: a preclinical study - Download this document for free, or read online. Document in PDF available to download.

Basic Research in Cardiology

, Volume 106, Issue 6, pp 1283–1297

First Online: 28 September 2011Received: 11 March 2011Revised: 08 August 2011Accepted: 05 September 2011

Abstract

Heart failure following acute myocardial infarction AMI is a major cause of morbidity and mortality. Our previous observation that injection of apoptotic peripheral blood mononuclear cell PBMC suspensions was able to restore long-term cardiac function in a rat AMI model prompted us to study the effect of soluble factors derived from apoptotic PBMC on ventricular remodelling after AMI. Cell culture supernatants derived from irradiated apoptotic peripheral blood mononuclear cells APOSEC were collected and injected as a single dose intravenously after myocardial infarction in an experimental AMI rat model and in a porcine closed chest reperfused AMI model. Magnetic resonance imaging MRI and echocardiography were used to quantitate cardiac function. Analysis of soluble factors present in APOSEC was performed by enzyme-linked immunosorbent assay ELISA and activation of signalling cascades in human cardiomyocytes by APOSEC in vitro was studied by immunoblot analysis. Intravenous administration of a single dose of APOSEC resulted in a reduction of scar tissue formation in both AMI models. In the porcine reperfused AMI model, APOSEC led to higher values of ejection fraction 57.0 vs. 40.5%, p < 0.01, a better cardiac output 4.0 vs. 2.4 l-min, p < 0.001 and a reduced extent of infarction size 12.6 vs. 6.9%, p < 0.02 as determined by MRI. Exposure of primary human cardiac myocytes with APOSEC in vitro triggered the activation of pro-survival signalling-cascades AKT, Erk1-2, CREB, c-Jun, increased anti-apoptotic gene products Bcl-2, BAG1 and protected them from starvation-induced cell death. Intravenous infusion of culture supernatant of apoptotic PBMC attenuates myocardial remodelling in experimental AMI models. This effect is probably due to the activation of pro-survival signalling cascades in the affected cardiomyocytes.

KeywordsApoptosis Myocardial infarction Cardioprotection Ischaemia-reperfusion M. Lichtenauer and M. Mildner contributed equally to this work.

Electronic supplementary materialThe online version of this article doi:10.1007-s00395-011-0224-6 contains supplementary material, which is available to authorized users.

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Author: Michael Lichtenauer - Michael Mildner - Konrad Hoetzenecker - Matthias Zimmermann - Bruno Karl Podesser - Wolfgang Sipos -

Source: https://link.springer.com/







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