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European Heart Journal 2002 23(11):849-857; doi:10.1053/euhj.2001.2963
Copyright © 2002 by the European Society of Cardiology.
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Dissociation of cardiomyocyte apoptosis and dedifferentiation in infarct border zones

G.D. Dispersyna, L. Mesottenb, B. Meurisc, A. Maesb, L. Mortelmansb, W. Flamengc, F. Ramaekersa and M. Borgersa,f1

a Department of Molecular Cell Biology, Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, The Netherlands
b Department of Nuclear Medicine, Gasthuisberg University Hospital, Catholic University Leuven, Leuven, Belgium
c Centre for Experimental Surgery and Anaesthesiology, Catholic University Leuven, Leuven, Belgium

revised August 7, 2001; accepted August 15, 2001

Abstract

Aims Cardiomyocyte apoptosis is known to occur in infarct border zones, where cardiomyocyte dedifferentiation, as seen in hibernating myocardium, can also be observed. The aim of the study is to determine whether dedifferentiated cardiomyocytes represent a population of cells stably surviving or undergoing apoptosis.

Methods and Results Microinfarctions were induced in sheep (n=8) by intracoronary injection of polymer macrobeads. The sheep were killed when cardiac function was gradually decreased (ejection fraction 37±6%, mean±SEM), but not earlier than 6 weeks after embolization. Transmural biopsies were taken from embolized and remote areas, based on flow measurements with positron emission tomography. Cells were classified as dedifferentiated when sarcomere content was depleted by >10% and glycogen content increased. Apoptosis was detected using the Tdt-mediated nick-end labelling (TUNEL) method and activated caspase-3 immunolabelling. Dedifferentiated cardiomyocytes were identified by morphology and by immunohistochemical evaluation of dedifferentiation related expression patterns of desmin, titin, cardiotin and {alpha}-smooth muscle actin. Cardiomyocyte apoptosis was detected in both the infarction border zones and remote areas. Dedifferentiated cardiomyocytes accounted for up to 30% of the cells in embolized areas and were almost exclusively non-apoptotic.

Conclusion In embolization induced microinfarcted tissue, dedifferentiated cardiomyocytes are preferentially spared to undergo apoptosis. It is hypothesized that dedifferentiated cardiomyocytes and apoptotic cardiomyocytes represent two different cell populations. The dedifferentiated cells can be considered as stable surviving cells. Copyright 2001 The European Society of Cardiology. Published by Elsevier Science Ltd. All rights reserved

Key Words: Apoptosis, hibernation, myocardial infarction, immunohistochemistry, remodelling

f1 Correspondence: Marcel Borgers, PhD, Department Molecular Cell Biology, CARIM, Maastricht University, Universiteitssingel 50, P.O. Box 616, 6200 MD Maastricht, The Netherlands.

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