Publication details

APOPTOSIS OF CARDIAC MYOCYTES AND ENDOTHELIAL CELLS CONTRIBUTES TO PATHOGENESIS OF DOXORUBICIN-INDUCED CARDIOMYOPATHY IN SPONTANEOUSLY HYPERTENSIVE RATS

Authors

UMLAUF Jozef KUCHTÍČKOVÁ Šárka SLANÁ B. KOTALA Vladimír

Year of publication 2002
Type Article in Periodical
Magazine / Source Biomarkers and Enviroment
MU Faculty or unit

Faculty of Medicine

Citation
Field Genetics and molecular biology
Keywords Doxorubicin; Apoptosis; Endothelial cells; Cardiac myocytes; Caspase-3; TUNEL assay
Description The aim of our study was to detect apoptosis of cardiac myocytes and endothelial cells of the left ventricular myocardium in SHR. We used the TUNEL assay and caspase-3 antibodies to assess critical steps in the pathways of active cell death, which involve rapid proteolysis and final DNA fragmentation. The spontaneously hypertensive rats were treated with doxorubucin for 8 weeks. The left ventricular myocardium was harvested after the 1st, 2nd, 3rd, 4th and 8th weeks. The histological examination revealed a rapid onset of nuclear caspase- 3 positivity as well as TUNEL positivity after 7 days of treatment, which continued in all the periods investigated. We also found caspase-3 positive nuclei in cardiac myocytes after the 1st week of doxorubicin treatment. The number of TUNEL positive cardiomyocytes rose after the second week of treatment and peaked after 4 weeks of treatment. Our data show that apoptosis of endothelial cells and cardiac myocytes plays a critical role in the pathogenesis of doxorubicin induced cardiomyopathy.
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