TY  - JOUR
AU  - Pajović, Vladislav
AU  - Kovacshazi, Csenger
AU  - Kosić, Marija
AU  - Vasić, Marko
AU  - Dukić, Ljiljana
AU  - Brenner, Gabor B.
AU  - Giricz, Zoltan
AU  - Bajić, Dragana
AU  - Ferdinandy, Peter
AU  - Japundžić-Žigon, Nina
PY  - 2021
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1447
UR  - http://intor.torlakinstitut.com/handle/123456789/807
AB  - 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.
PB  - Academic Press Inc Elsevier Science, San Diego
T2  - Toxicology and Applied Pharmacology
T1  - Phenomapping for classification of doxorubicin-induced cardiomyopathy in rats
VL  - 423
DO  - 10.1016/j.taap.2021.115579
ER  - 

@article{
author = "Pajović, Vladislav and Kovacshazi, Csenger and Kosić, Marija and Vasić, Marko and Dukić, Ljiljana and Brenner, Gabor B. and Giricz, Zoltan and Bajić, Dragana and Ferdinandy, Peter and Japundžić-Žigon, Nina",
year = "2021",
abstract = "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.",
publisher = "Academic Press Inc Elsevier Science, San Diego",
journal = "Toxicology and Applied Pharmacology",
title = "Phenomapping for classification of doxorubicin-induced cardiomyopathy in rats",
volume = "423",
doi = "10.1016/j.taap.2021.115579"
}

Pajović, V., Kovacshazi, C., Kosić, M., Vasić, M., Dukić, L., Brenner, G. B., Giricz, Z., Bajić, D., Ferdinandy, P.,& Japundžić-Žigon, N.. (2021). Phenomapping for classification of doxorubicin-induced cardiomyopathy in rats. in Toxicology and Applied Pharmacology
Academic Press Inc Elsevier Science, San Diego., 423.
https://doi.org/10.1016/j.taap.2021.115579

Pajović V, Kovacshazi C, Kosić M, Vasić M, Dukić L, Brenner GB, Giricz Z, Bajić D, Ferdinandy P, Japundžić-Žigon N. Phenomapping for classification of doxorubicin-induced cardiomyopathy in rats. in Toxicology and Applied Pharmacology. 2021;423.
doi:10.1016/j.taap.2021.115579 .

Pajović, Vladislav, Kovacshazi, Csenger, Kosić, Marija, Vasić, Marko, Dukić, Ljiljana, Brenner, Gabor B., Giricz, Zoltan, Bajić, Dragana, Ferdinandy, Peter, Japundžić-Žigon, Nina, "Phenomapping for classification of doxorubicin-induced cardiomyopathy in rats" in Toxicology and Applied Pharmacology, 423 (2021),
https://doi.org/10.1016/j.taap.2021.115579 . .