Phenomapping for classification of doxorubicin-induced cardiomyopathy in rats
| Autor: | Marko Vasić, Csenger Kovácsházi, Marija Kosić, Vladislav Pajović, Gábor B. Brenner, Zoltán Giricz, Péter Ferdinandy, Dragana Bajic, Ljiljana Đukić, Nina Japundžić-Žigon |
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| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Male medicine.medical_specialty Baroreceptor medicine.medical_treatment Cardiomyopathy Toxicology 03 medical and health sciences Random Allocation 0302 clinical medicine Internal medicine medicine Animals Doxorubicin Rats Wistar Saline Pharmacology Ejection fraction Antibiotics Antineoplastic business.industry Chromosome Mapping Histology medicine.disease 3. Good health Rats 030104 developmental biology 030220 oncology & carcinogenesis cardiovascular system Cardiology MYH7 MYH6 business Cardiomyopathies medicine.drug |
| Zdroj: | Toxicology and applied pharmacology. 423 |
| ISSN: | 1096-0333 |
| Popis: | Cardiomyopathy resistant to treatment is the most serious adverse effect of doxorubicin (dox). The mechanisms of dox-induced cardiomyopathy (DCM) have been extensively studied in dilated forms of DCM. However, efficient treatment did not emerge. The aim of the present work was to revisit the experimental model of DCM in rats, to define phenotype/s and associate them to the changes in cardiac transcriptome. Male Wistar rats equipped with radiotelemetry device, were randomized in DOX group (5 mg/0,5 mL/kg, IV dox; n = 18) and CONT group (0,5 mL/kg IV saline; n = 6). Echocardiography, autonomic spectral markers and baroreceptor reflex evaluation was performed prior to, and after treatment. Blood samples were collected at the end of experimentation. Cardiac, renal and hepatic tissues were analysed post-mortem by histology. Changes in expression of key cardiac genes affected by dox were assessed by RT-qPCR. Phenotypes were identified by clustering non-redundant features using four different algorithms averaged by evidence accumulation cluster technique. The results emphasize the existence of two major phenotypes of DCM with comparably high mortality rates: phenotype 1 characterized by, left ventricular (LV) dilatation, thinning of LV posterior wall, reduced LV ejection fraction (LVEF) and fractional shortening (LVFS), decreased HR variability (HRV), decreased baroreceptor effectiveness index (BEI) and increased NT-proBNP; and phenotype 2 with LV hypertrophy - increased LV mass, preserved LVEF, LVFS, no changes in HRV and BEI and moderate NT-proBNP increase. Both phenotypes exhibited a genetic shift to a new-born program. |
| Databáze: | OpenAIRE |
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