APOPTOSIS OF CARDIAC MYOCYTES AND ENDOTHELIAL CELLS CONTRIBUTES TO PATHOGENESIS OF DOXORUBICIN-INDUCED CARDIOMYOPATHY IN SPONTANEOUSLY HYPERTENSIVE RATS
| Authors | |
|---|---|
| Year of publication | 2002 |
| Type | Article in Periodical |
| Magazine / Source | Biomarkers and Enviroment |
| MU Faculty or unit | |
| 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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