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Dissociation of cardiomyocyte apoptosis and dedifferentiation in infarct border zones
- Source :
- European Heart Journal, 23, 849-857. Oxford University Press
- Publication Year :
- 2002
-
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 a-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.
- Subjects :
- Pathology
medicine.medical_specialty
Cell Survival
Population
Myocardial Infarction
Caspase 3
Apoptosis
DNA Fragmentation
Sarcomere
Fluorodeoxyglucose F18
medicine
In Situ Nick-End Labeling
Animals
education
Hibernating myocardium
Myocardial Stunning
Myocardial stunning
education.field_of_study
Enzyme Precursors
TUNEL assay
Sheep
business.industry
Myocardium
Heart
medicine.disease
Actins
Caspases
Desmin
Female
medicine.symptom
Radiopharmaceuticals
Cardiology and Cardiovascular Medicine
business
Tomography, Emission-Computed
Subjects
Details
- Language :
- English
- ISSN :
- 0195668X
- Volume :
- 23
- Database :
- OpenAIRE
- Journal :
- European Heart Journal
- Accession number :
- edsair.doi.dedup.....2d6a1d7185172ecc23911da43beb999b