TY  - CONF
AU  - Novković, Mirjana
AU  - Vasić, Marko
AU  - Jasnić, Jovana
AU  - Milošević, Emilija
AU  - Milovanović, Mina
AU  - Savić, Slobodan
AU  - Kojić, Snežana
PY  - 2023
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/2114
AB  - Introduction: Ankyrin Repeat Domain 2 (ANKRD2) is expressed in skeletal muscle, where plays a role in
muscle development, differentiation and adaptation to stress. Human skeletal muscle consists of three
major fiber types: type 1 (slow-twitch, oxidative), type 2A (fast-twitch, oxidative) and type 2X (fast-twitch,
glycolytic). ANKRD2 is reported to be primarily expressed in type 1 myofibers. However, recent findings
on human single myofibers and our study of chicken muscles have shown that this protein may also be
expressed in type 2A fibers. Hence, our objective was to examine whether ANKRD2 is present in human
fast, type 2A muscle fibers using immunohistochemistry.
Methods: Samples of large leg musclessoleus, gastrocnemius, vastusintermedius and vastuslateralis were
obtained from human cadaveric tissue. Serial cryosections were independently stained with anti-ANKRD2
and antibodies for different myosin heavy chain isoforms (6H1 for type 2X, BF35 for type 1 and 2A, antiMHCs for type 1 and anti-MHCf for type 2A and 2X fibers). Immunostained tissues were analyzed by fluorescent microscopy.
Results: In addition to slow, type 1, ANKRD2 wasfound expressed in fast, type 2A myofibers, which both
have oxidative metabolism. Further, we did not observe ANDRD2 expression in glycolytic, type 2X
myiofibers. This pattern of ANKRD2 expression was consistent across all examined muscles.
Conclusion: Our resultsimplicate that the regulatory mechanism of ANKRD2 expression in human skeletal muscle is associated with oxidative metabolism, rather than muscle contraction speed.
PB  - Institute of Molecular Genetics and Genetic Engineering (IMGGE), University of Belgrade
C3  - CoMBoS2 – the Second Congress of Molecular Biologists of Serbia, Abstract Book – Trends in Molecular Biology, Special issue 06-08 October 2023, Belgrade, Serbia
T1  - Determination of muscle fiber types expressing ANKRD2
EP  - 155
SP  - 155
UR  - https://hdl.handle.net/21.15107/rcub_imagine_2114
ER  - 

@conference{
author = "Novković, Mirjana and Vasić, Marko and Jasnić, Jovana and Milošević, Emilija and Milovanović, Mina and Savić, Slobodan and Kojić, Snežana",
year = "2023",
abstract = "Introduction: Ankyrin Repeat Domain 2 (ANKRD2) is expressed in skeletal muscle, where plays a role in
muscle development, differentiation and adaptation to stress. Human skeletal muscle consists of three
major fiber types: type 1 (slow-twitch, oxidative), type 2A (fast-twitch, oxidative) and type 2X (fast-twitch,
glycolytic). ANKRD2 is reported to be primarily expressed in type 1 myofibers. However, recent findings
on human single myofibers and our study of chicken muscles have shown that this protein may also be
expressed in type 2A fibers. Hence, our objective was to examine whether ANKRD2 is present in human
fast, type 2A muscle fibers using immunohistochemistry.
Methods: Samples of large leg musclessoleus, gastrocnemius, vastusintermedius and vastuslateralis were
obtained from human cadaveric tissue. Serial cryosections were independently stained with anti-ANKRD2
and antibodies for different myosin heavy chain isoforms (6H1 for type 2X, BF35 for type 1 and 2A, antiMHCs for type 1 and anti-MHCf for type 2A and 2X fibers). Immunostained tissues were analyzed by fluorescent microscopy.
Results: In addition to slow, type 1, ANKRD2 wasfound expressed in fast, type 2A myofibers, which both
have oxidative metabolism. Further, we did not observe ANDRD2 expression in glycolytic, type 2X
myiofibers. This pattern of ANKRD2 expression was consistent across all examined muscles.
Conclusion: Our resultsimplicate that the regulatory mechanism of ANKRD2 expression in human skeletal muscle is associated with oxidative metabolism, rather than muscle contraction speed.",
publisher = "Institute of Molecular Genetics and Genetic Engineering (IMGGE), University of Belgrade",
journal = "CoMBoS2 – the Second Congress of Molecular Biologists of Serbia, Abstract Book – Trends in Molecular Biology, Special issue 06-08 October 2023, Belgrade, Serbia",
title = "Determination of muscle fiber types expressing ANKRD2",
pages = "155-155",
url = "https://hdl.handle.net/21.15107/rcub_imagine_2114"
}

Novković, M., Vasić, M., Jasnić, J., Milošević, E., Milovanović, M., Savić, S.,& Kojić, S.. (2023). Determination of muscle fiber types expressing ANKRD2. in CoMBoS2 – the Second Congress of Molecular Biologists of Serbia, Abstract Book – Trends in Molecular Biology, Special issue 06-08 October 2023, Belgrade, Serbia
Institute of Molecular Genetics and Genetic Engineering (IMGGE), University of Belgrade., 155-155.
https://hdl.handle.net/21.15107/rcub_imagine_2114

Novković M, Vasić M, Jasnić J, Milošević E, Milovanović M, Savić S, Kojić S. Determination of muscle fiber types expressing ANKRD2. in CoMBoS2 – the Second Congress of Molecular Biologists of Serbia, Abstract Book – Trends in Molecular Biology, Special issue 06-08 October 2023, Belgrade, Serbia. 2023;:155-155.
https://hdl.handle.net/21.15107/rcub_imagine_2114 .

Novković, Mirjana, Vasić, Marko, Jasnić, Jovana, Milošević, Emilija, Milovanović, Mina, Savić, Slobodan, Kojić, Snežana, "Determination of muscle fiber types expressing ANKRD2" in CoMBoS2 – the Second Congress of Molecular Biologists of Serbia, Abstract Book – Trends in Molecular Biology, Special issue 06-08 October 2023, Belgrade, Serbia (2023):155-155,
https://hdl.handle.net/21.15107/rcub_imagine_2114 .

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
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 . .

TY  - THES
AU  - Vasić, Marko
PY  - 2019
UR  - http://eteze.bg.ac.rs/application/showtheses?thesesId=7016
UR  - https://nardus.mpn.gov.rs/handle/123456789/11639
UR  - https://fedorabg.bg.ac.rs/fedora/get/o:20624/bdef:Content/download
UR  - http://vbs.rs/scripts/cobiss?command=DISPLAY&base=70036&RID=51736335
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/58
AB  - Antraciklinski antibiotik doksorubicin pokazao se u višedecenijskoj kliničkoj praksi kao efikasan lek u terapiji brojnih maligniteta. Međutim, njegovu primenu ozbiljno sprečava pojava organske, a posebno srčane toksičnosti. Doksorubicinska kardiomiopatija razvija se najranije 30 dana, a nekada i nakon više godina od terapije doksorubicinom, rezistentna je na postojeću terapiju i ima veliku stopu smrtnosti. Premda su mehanizmi doksorubicinske kardiomiopatije dobro izučeni, još uvek ne postoje efikasna prevencija ni terapija. Zato je primena doksorbicina u kliničkoj praksi prihvatljiva samo uz stalni monitoring rada srca. U kardiološkoj praksi, varijabilitet srčane frekvencije (HRV) i senzitivnost arterijskog baroreceptorskog refleksa (sBRS) koriste se u prognostičke svrhe kod hipertenzije i ishemijske bolesti srca. U ovom radu ispitivani su dijagnostički i prognostički značaj HRV i sBRS za rànō otkrivanje kardiomiopatije prouzrokovane doksorubicinom i upoređivanje sa standardnim metodama – ehokardiografijom i serumskim markerima oštećenja kardiomiocita – srčanim troponinima. S obzirom na to da je uloga β-adrenergičkih receptora (β-AR) u nastanku srčane slabosti dobro poznata, pratili smo i ekspresiju srčanih β1- i β2-AR kod pacova tretiranih doksorubicinom, i poredili sa promenama HRV. Eksperimenti su izvedeni na odraslim mužjacima pacova Wistar soja, kojima je u femoralnu arteriju plasiran polietilenski kateter za registrovanje hemodinamskih parametara i uzorkovanje krvi. Eksperimentalnoj (DOX, n = 50) grupi, aplikovan je doksorubicin u kumulativnoj dozi od 15 mg/kg. Kontrolnoj grupi (CONT, n = 18) aplikovan je fiziološki rastvor u istoj zapremini. Procenjivana je opšta toksičnost doksorubicina i praćeni su hemodinamski ehokardiografski paramentri: pre tretmana, 35. dana (DOX35) i 70. dana (DOX70) nakon aplikacije doksorubicina. HRV analiziran je upotrebom nekoliko metóda: spektralne analize (Hilbert-Huangova transformacija), Poenkareovih dijagrama, aproksimativne entropije i entropije uzorka...
AB  - Anthracycline antibiotic doxorubicin, used in clinical practice for several decades, has been shown as effective antineoplastic drug. Unfortunately, its usage is hindered due to multiple organotoxicity and especially cardiac toxicity. Doxorubicin-induced cardiomyopathy may develop 30 days, or even several years after following treatment. It is resistant to treatment, and has very high mortality rate. Although the mechanisms of doxorubicin-induced cardiomyopathy are well studied, there are still no effective treatment and prevention. Hence, the usage of doxorubicin in clinical practice is acceptable merely under close monitoring of cardiac function. In cardiology practice, heart rate variability (HRV) and baroreflex sensitivity (sBRS) are used as prognostic markers in hypertension and ischemic heart disease. Herein, we evaluated and compared diagnostic and prognostic values of HRV and sBRS in doxorubicin-induced cardiomyopathy to standard echocardiographic and serum cardiac troponin T and I methods. In addition, considering the pathophysiological role of β-adrenergic receptors (β-AR) in heart failure, we scrutinised the expression of β1- and β2-AR in doxorubicin-induced cardiomyopathy and its association to HRV changes. Experiments were performed on adult male Wistar rats, replete with femoral arterial catheter for blood pressure recording and blood sampling. Doxorubicin (DOX, n = 50) or saline (CONT, n = 18) were applied to rats in cumulative dose of 15 mg/kg (i.p.). General toxicity, cardiovascular hemodynamics and echocardiography were assessed before treatment, 35 days and 70 days after treatment. HRV and blood pressure variability (BPV) were evaluated by several methods (Hilbert-Huang frequency analysis, Poincaré plots, approximate entropy and sample entropy). The sequence method was used to evaluate sBRS. Levels of cardiac troponin T and I were measured by ECLIA method. β1-AR and β2-AR gene expression was measured by RT-qPCR...
PB  - Univerzitet u Beogradu, Medicinski fakultet
T1  - Varijabilitet srčane frekvencije i ekspresija ß-adrenergičkih receptora u kardiomiopatiji izazvanoj doksorubicinom
T1  - Heart rate variability and ß-adrenergic receptor gene expression in doxorubicin-induced cardiomyopathy
UR  - https://hdl.handle.net/21.15107/rcub_nardus_11639
ER  - 

@phdthesis{
author = "Vasić, Marko",
year = "2019",
abstract = "Antraciklinski antibiotik doksorubicin pokazao se u višedecenijskoj kliničkoj praksi kao efikasan lek u terapiji brojnih maligniteta. Međutim, njegovu primenu ozbiljno sprečava pojava organske, a posebno srčane toksičnosti. Doksorubicinska kardiomiopatija razvija se najranije 30 dana, a nekada i nakon više godina od terapije doksorubicinom, rezistentna je na postojeću terapiju i ima veliku stopu smrtnosti. Premda su mehanizmi doksorubicinske kardiomiopatije dobro izučeni, još uvek ne postoje efikasna prevencija ni terapija. Zato je primena doksorbicina u kliničkoj praksi prihvatljiva samo uz stalni monitoring rada srca. U kardiološkoj praksi, varijabilitet srčane frekvencije (HRV) i senzitivnost arterijskog baroreceptorskog refleksa (sBRS) koriste se u prognostičke svrhe kod hipertenzije i ishemijske bolesti srca. U ovom radu ispitivani su dijagnostički i prognostički značaj HRV i sBRS za rànō otkrivanje kardiomiopatije prouzrokovane doksorubicinom i upoređivanje sa standardnim metodama – ehokardiografijom i serumskim markerima oštećenja kardiomiocita – srčanim troponinima. S obzirom na to da je uloga β-adrenergičkih receptora (β-AR) u nastanku srčane slabosti dobro poznata, pratili smo i ekspresiju srčanih β1- i β2-AR kod pacova tretiranih doksorubicinom, i poredili sa promenama HRV. Eksperimenti su izvedeni na odraslim mužjacima pacova Wistar soja, kojima je u femoralnu arteriju plasiran polietilenski kateter za registrovanje hemodinamskih parametara i uzorkovanje krvi. Eksperimentalnoj (DOX, n = 50) grupi, aplikovan je doksorubicin u kumulativnoj dozi od 15 mg/kg. Kontrolnoj grupi (CONT, n = 18) aplikovan je fiziološki rastvor u istoj zapremini. Procenjivana je opšta toksičnost doksorubicina i praćeni su hemodinamski ehokardiografski paramentri: pre tretmana, 35. dana (DOX35) i 70. dana (DOX70) nakon aplikacije doksorubicina. HRV analiziran je upotrebom nekoliko metóda: spektralne analize (Hilbert-Huangova transformacija), Poenkareovih dijagrama, aproksimativne entropije i entropije uzorka..., Anthracycline antibiotic doxorubicin, used in clinical practice for several decades, has been shown as effective antineoplastic drug. Unfortunately, its usage is hindered due to multiple organotoxicity and especially cardiac toxicity. Doxorubicin-induced cardiomyopathy may develop 30 days, or even several years after following treatment. It is resistant to treatment, and has very high mortality rate. Although the mechanisms of doxorubicin-induced cardiomyopathy are well studied, there are still no effective treatment and prevention. Hence, the usage of doxorubicin in clinical practice is acceptable merely under close monitoring of cardiac function. In cardiology practice, heart rate variability (HRV) and baroreflex sensitivity (sBRS) are used as prognostic markers in hypertension and ischemic heart disease. Herein, we evaluated and compared diagnostic and prognostic values of HRV and sBRS in doxorubicin-induced cardiomyopathy to standard echocardiographic and serum cardiac troponin T and I methods. In addition, considering the pathophysiological role of β-adrenergic receptors (β-AR) in heart failure, we scrutinised the expression of β1- and β2-AR in doxorubicin-induced cardiomyopathy and its association to HRV changes. Experiments were performed on adult male Wistar rats, replete with femoral arterial catheter for blood pressure recording and blood sampling. Doxorubicin (DOX, n = 50) or saline (CONT, n = 18) were applied to rats in cumulative dose of 15 mg/kg (i.p.). General toxicity, cardiovascular hemodynamics and echocardiography were assessed before treatment, 35 days and 70 days after treatment. HRV and blood pressure variability (BPV) were evaluated by several methods (Hilbert-Huang frequency analysis, Poincaré plots, approximate entropy and sample entropy). The sequence method was used to evaluate sBRS. Levels of cardiac troponin T and I were measured by ECLIA method. β1-AR and β2-AR gene expression was measured by RT-qPCR...",
publisher = "Univerzitet u Beogradu, Medicinski fakultet",
title = "Varijabilitet srčane frekvencije i ekspresija ß-adrenergičkih receptora u kardiomiopatiji izazvanoj doksorubicinom, Heart rate variability and ß-adrenergic receptor gene expression in doxorubicin-induced cardiomyopathy",
url = "https://hdl.handle.net/21.15107/rcub_nardus_11639"
}

Vasić, M.. (2019). Varijabilitet srčane frekvencije i ekspresija ß-adrenergičkih receptora u kardiomiopatiji izazvanoj doksorubicinom. 
Univerzitet u Beogradu, Medicinski fakultet..
https://hdl.handle.net/21.15107/rcub_nardus_11639

Vasić M. Varijabilitet srčane frekvencije i ekspresija ß-adrenergičkih receptora u kardiomiopatiji izazvanoj doksorubicinom. 2019;.
https://hdl.handle.net/21.15107/rcub_nardus_11639 .

Vasić, Marko, "Varijabilitet srčane frekvencije i ekspresija ß-adrenergičkih receptora u kardiomiopatiji izazvanoj doksorubicinom" (2019),
https://hdl.handle.net/21.15107/rcub_nardus_11639 .

TY  - JOUR
AU  - Vasić, Marko
AU  - Loncar-Turukalo, Tatjana
AU  - Tasić, Tatjana
AU  - Matić, Marija
AU  - Glumac, Sofija
AU  - Bajić, Dragana
AU  - Popović, Branka
AU  - Japundžić-Žigon, Nina
PY  - 2019
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1291
AB  - Using comprehensive analysis of heart rate (HRV) and blood pressure (BPV) short-term variability we estimated the time course of changes of autonomic nervous system remodeling in two stages of doxorubicin-induced cardiomyopathy (DCM). We also investigated the level of gene expression of cardiac beta-1 (beta-1AR) and beta-2 (beta-2AR) adrenoceptors. Experiments were performed in adult male Wistar rats equipped with indwelling catheters for BP recording and blood withdrawal. A 15 mg/kg total cumulative dose of doxorubicin was injected i.p. to rats to induce DCM or saline for control (n = 18). Rats were assessed for general toxicity, cardiovascular hemodynamic and echocardiography before treatment (n = 6), 35 days (DOX35; n = 6) and 70 days (DOX70; n = 6) post-treatment. HRV was evaluated by spectral analysis, Poincare plots, sample and approximate entropy. Expression of beta-1AR and beta-2AR mRNA was evaluated by RT-qPCR. Doxorubicin-treated rats exhibited poor general condition and lower survival than saline-treated rats. In DOX35 rats, there were no echocardiography signs of decompensation, no increase in serum cardiac troponins, but there was an increase of HRV and decrease of HR complexity. In these rats typical microscopic signs of cardiotoxicity were seen along with over-expression of beta-1AR mRNA. 70 days post-treatment echocardiography revealed signs of decompensation and serum cardiac troponin T was increased. At this stage BPV decreased. In conclusion, HRV increase matches transient over expression of cardiac beta-1AR mRNA in compensate stage of DCM while decompensate stage of DCM is characterized by a decrease of BPV and no changes in beta-1AR and beta-2AR gene expression.
PB  - Academic Press Inc Elsevier Science, San Diego
T2  - Toxicology and Applied Pharmacology
T1  - Cardiovascular variability and beta-ARs gene expression at two stages of doxorubicin - Induced cardiomyopathy
EP  - 51
SP  - 43
VL  - 362
DO  - 10.1016/j.taap.2018.10.015
ER  - 

@article{
author = "Vasić, Marko and Loncar-Turukalo, Tatjana and Tasić, Tatjana and Matić, Marija and Glumac, Sofija and Bajić, Dragana and Popović, Branka and Japundžić-Žigon, Nina",
year = "2019",
abstract = "Using comprehensive analysis of heart rate (HRV) and blood pressure (BPV) short-term variability we estimated the time course of changes of autonomic nervous system remodeling in two stages of doxorubicin-induced cardiomyopathy (DCM). We also investigated the level of gene expression of cardiac beta-1 (beta-1AR) and beta-2 (beta-2AR) adrenoceptors. Experiments were performed in adult male Wistar rats equipped with indwelling catheters for BP recording and blood withdrawal. A 15 mg/kg total cumulative dose of doxorubicin was injected i.p. to rats to induce DCM or saline for control (n = 18). Rats were assessed for general toxicity, cardiovascular hemodynamic and echocardiography before treatment (n = 6), 35 days (DOX35; n = 6) and 70 days (DOX70; n = 6) post-treatment. HRV was evaluated by spectral analysis, Poincare plots, sample and approximate entropy. Expression of beta-1AR and beta-2AR mRNA was evaluated by RT-qPCR. Doxorubicin-treated rats exhibited poor general condition and lower survival than saline-treated rats. In DOX35 rats, there were no echocardiography signs of decompensation, no increase in serum cardiac troponins, but there was an increase of HRV and decrease of HR complexity. In these rats typical microscopic signs of cardiotoxicity were seen along with over-expression of beta-1AR mRNA. 70 days post-treatment echocardiography revealed signs of decompensation and serum cardiac troponin T was increased. At this stage BPV decreased. In conclusion, HRV increase matches transient over expression of cardiac beta-1AR mRNA in compensate stage of DCM while decompensate stage of DCM is characterized by a decrease of BPV and no changes in beta-1AR and beta-2AR gene expression.",
publisher = "Academic Press Inc Elsevier Science, San Diego",
journal = "Toxicology and Applied Pharmacology",
title = "Cardiovascular variability and beta-ARs gene expression at two stages of doxorubicin - Induced cardiomyopathy",
pages = "51-43",
volume = "362",
doi = "10.1016/j.taap.2018.10.015"
}

Vasić, M., Loncar-Turukalo, T., Tasić, T., Matić, M., Glumac, S., Bajić, D., Popović, B.,& Japundžić-Žigon, N.. (2019). Cardiovascular variability and beta-ARs gene expression at two stages of doxorubicin - Induced cardiomyopathy. in Toxicology and Applied Pharmacology
Academic Press Inc Elsevier Science, San Diego., 362, 43-51.
https://doi.org/10.1016/j.taap.2018.10.015

Vasić M, Loncar-Turukalo T, Tasić T, Matić M, Glumac S, Bajić D, Popović B, Japundžić-Žigon N. Cardiovascular variability and beta-ARs gene expression at two stages of doxorubicin - Induced cardiomyopathy. in Toxicology and Applied Pharmacology. 2019;362:43-51.
doi:10.1016/j.taap.2018.10.015 .

Vasić, Marko, Loncar-Turukalo, Tatjana, Tasić, Tatjana, Matić, Marija, Glumac, Sofija, Bajić, Dragana, Popović, Branka, Japundžić-Žigon, Nina, "Cardiovascular variability and beta-ARs gene expression at two stages of doxorubicin - Induced cardiomyopathy" in Toxicology and Applied Pharmacology, 362 (2019):43-51,
https://doi.org/10.1016/j.taap.2018.10.015 . .

TY  - JOUR
AU  - Japundžić-Žigon, Nina
AU  - Sarenac, Olivera
AU  - Lozić, Maja
AU  - Vasić, Marko
AU  - Tasić, Tatjana
AU  - Bajić, Dragana
AU  - Kanjuh, Vladimir
AU  - Murphy, David
PY  - 2018
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1170
AB  - Sudden death is a major health problem all over the world. The most common causes of sudden death are cardiac but there are also other causes such as neurological conditions (stroke, epileptic attacks and brain trauma), drugs, catecholamine toxicity, etc. A common feature of all these diverse pathologies underlying sudden death is the imbalance of the autonomic nervous system control of the cardiovascular system. This paper reviews different pathologies underlying sudden death with emphasis on the autonomic nervous system contribution, possibilities of early diagnosis and prognosis of sudden death using various clinical markers including autonomic markers (heart rate variability and baroreflex sensitivity), present possibilities of management and promising prevention by electrical neuromodulation.
PB  - Oxford Univ Press, Oxford
T2  - European Journal of Preventive Cardiology
T1  - Sudden death: Neurogenic causes, prediction and prevention
EP  - 39
IS  - 1
SP  - 29
VL  - 25
DO  - 10.1177/2047487317736827
ER  - 

@article{
author = "Japundžić-Žigon, Nina and Sarenac, Olivera and Lozić, Maja and Vasić, Marko and Tasić, Tatjana and Bajić, Dragana and Kanjuh, Vladimir and Murphy, David",
year = "2018",
abstract = "Sudden death is a major health problem all over the world. The most common causes of sudden death are cardiac but there are also other causes such as neurological conditions (stroke, epileptic attacks and brain trauma), drugs, catecholamine toxicity, etc. A common feature of all these diverse pathologies underlying sudden death is the imbalance of the autonomic nervous system control of the cardiovascular system. This paper reviews different pathologies underlying sudden death with emphasis on the autonomic nervous system contribution, possibilities of early diagnosis and prognosis of sudden death using various clinical markers including autonomic markers (heart rate variability and baroreflex sensitivity), present possibilities of management and promising prevention by electrical neuromodulation.",
publisher = "Oxford Univ Press, Oxford",
journal = "European Journal of Preventive Cardiology",
title = "Sudden death: Neurogenic causes, prediction and prevention",
pages = "39-29",
number = "1",
volume = "25",
doi = "10.1177/2047487317736827"
}

Japundžić-Žigon, N., Sarenac, O., Lozić, M., Vasić, M., Tasić, T., Bajić, D., Kanjuh, V.,& Murphy, D.. (2018). Sudden death: Neurogenic causes, prediction and prevention. in European Journal of Preventive Cardiology
Oxford Univ Press, Oxford., 25(1), 29-39.
https://doi.org/10.1177/2047487317736827

Japundžić-Žigon N, Sarenac O, Lozić M, Vasić M, Tasić T, Bajić D, Kanjuh V, Murphy D. Sudden death: Neurogenic causes, prediction and prevention. in European Journal of Preventive Cardiology. 2018;25(1):29-39.
doi:10.1177/2047487317736827 .

Japundžić-Žigon, Nina, Sarenac, Olivera, Lozić, Maja, Vasić, Marko, Tasić, Tatjana, Bajić, Dragana, Kanjuh, Vladimir, Murphy, David, "Sudden death: Neurogenic causes, prediction and prevention" in European Journal of Preventive Cardiology, 25, no. 1 (2018):29-39,
https://doi.org/10.1177/2047487317736827 . .

TY  - JOUR
AU  - Cheah, Hoay Yan
AU  - Sarenac, Olivera
AU  - Arroyo, Juan J.
AU  - Vasić, Marko
AU  - Lozić, Maja
AU  - Glumac, Sofija
AU  - Hoe, See Ziau
AU  - Hindmarch, Charles Colin Thomas
AU  - Murphy, David
AU  - Kiew, Lik Voon
AU  - Lee, Hong Boon
AU  - Vicent, Maria J.
AU  - Chung, Lip Yong
AU  - Japundžić-Žigon, Nina
PY  - 2017
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1056
AB  - Conjugation of Doxorubicin (DOX) to N-(2-hydroxypropyl) methylacrylamide copolymer (HPMA) has significantly reduced the DOX-associated cardiotoxicity. However, the reports on the impact of HPMA-DOX conjugates on the cardiovascular system such as blood pressure (BP) and heart rate (HR) were in restrained animals using tail cuff and/or other methods that lacked the resolution and sensitivity. Herein, we employed radiotelemetric-spectral-echocardiography approach to further understand the in vivo cardiovascular hemodynamics and variability post administration of free DOX and HPMA-DOX. Rats implanted with radio-telemetry device were administered intravenously with DOX (5mg/kg), HPMA-DOX (5mg DOX equivalent/kg) and HPMA copolymer and subjected to continuous cardiovascular monitoring and echocardiography for 140 days. We found that DOX-treated rats had ruffled fur, reduced body weight (BW) and a low survival rate. Although BP and HR were normal, spectral analysis indicated that their BP and HR variabilities were reduced. All rats exhibited typical signs of cardiotoxicity at histopathology. In contrast, HPMA-DOX rats gained weight over time and survived. Although BP, HR and related variabilities were unaffected, the left ventricular end diastolic volume (EDV) of these rats, as well as of the HPMA copolymer-treated rats, was found increased at the end of observation period. Additionally, HPMA copolymer caused microscopic injury of the heart tissue. All of these suggest the necessity of caution when employing HPMA as carrier for prolonged drug delivery. The current study also indicates the potential of radiotelemetric-spectral-echocardiography approach for improved preclinical cardiovascular risk assessment of polymer-drug conjugate and other nano-sized-drug constructs.
PB  - Taylor & Francis Ltd, Abingdon
T2  - Nanotoxicology
T1  - Hemodynamic effects of HPMA copolymer based doxorubicin conjugate: A randomized controlled and comparative spectral study in conscious rats
EP  - 222
IS  - 2
SP  - 210
VL  - 11
DO  - 10.1080/17435390.2017.1285071
ER  - 

@article{
author = "Cheah, Hoay Yan and Sarenac, Olivera and Arroyo, Juan J. and Vasić, Marko and Lozić, Maja and Glumac, Sofija and Hoe, See Ziau and Hindmarch, Charles Colin Thomas and Murphy, David and Kiew, Lik Voon and Lee, Hong Boon and Vicent, Maria J. and Chung, Lip Yong and Japundžić-Žigon, Nina",
year = "2017",
abstract = "Conjugation of Doxorubicin (DOX) to N-(2-hydroxypropyl) methylacrylamide copolymer (HPMA) has significantly reduced the DOX-associated cardiotoxicity. However, the reports on the impact of HPMA-DOX conjugates on the cardiovascular system such as blood pressure (BP) and heart rate (HR) were in restrained animals using tail cuff and/or other methods that lacked the resolution and sensitivity. Herein, we employed radiotelemetric-spectral-echocardiography approach to further understand the in vivo cardiovascular hemodynamics and variability post administration of free DOX and HPMA-DOX. Rats implanted with radio-telemetry device were administered intravenously with DOX (5mg/kg), HPMA-DOX (5mg DOX equivalent/kg) and HPMA copolymer and subjected to continuous cardiovascular monitoring and echocardiography for 140 days. We found that DOX-treated rats had ruffled fur, reduced body weight (BW) and a low survival rate. Although BP and HR were normal, spectral analysis indicated that their BP and HR variabilities were reduced. All rats exhibited typical signs of cardiotoxicity at histopathology. In contrast, HPMA-DOX rats gained weight over time and survived. Although BP, HR and related variabilities were unaffected, the left ventricular end diastolic volume (EDV) of these rats, as well as of the HPMA copolymer-treated rats, was found increased at the end of observation period. Additionally, HPMA copolymer caused microscopic injury of the heart tissue. All of these suggest the necessity of caution when employing HPMA as carrier for prolonged drug delivery. The current study also indicates the potential of radiotelemetric-spectral-echocardiography approach for improved preclinical cardiovascular risk assessment of polymer-drug conjugate and other nano-sized-drug constructs.",
publisher = "Taylor & Francis Ltd, Abingdon",
journal = "Nanotoxicology",
title = "Hemodynamic effects of HPMA copolymer based doxorubicin conjugate: A randomized controlled and comparative spectral study in conscious rats",
pages = "222-210",
number = "2",
volume = "11",
doi = "10.1080/17435390.2017.1285071"
}

Cheah, H. Y., Sarenac, O., Arroyo, J. J., Vasić, M., Lozić, M., Glumac, S., Hoe, S. Z., Hindmarch, C. C. T., Murphy, D., Kiew, L. V., Lee, H. B., Vicent, M. J., Chung, L. Y.,& Japundžić-Žigon, N.. (2017). Hemodynamic effects of HPMA copolymer based doxorubicin conjugate: A randomized controlled and comparative spectral study in conscious rats. in Nanotoxicology
Taylor & Francis Ltd, Abingdon., 11(2), 210-222.
https://doi.org/10.1080/17435390.2017.1285071

Cheah HY, Sarenac O, Arroyo JJ, Vasić M, Lozić M, Glumac S, Hoe SZ, Hindmarch CCT, Murphy D, Kiew LV, Lee HB, Vicent MJ, Chung LY, Japundžić-Žigon N. Hemodynamic effects of HPMA copolymer based doxorubicin conjugate: A randomized controlled and comparative spectral study in conscious rats. in Nanotoxicology. 2017;11(2):210-222.
doi:10.1080/17435390.2017.1285071 .

Cheah, Hoay Yan, Sarenac, Olivera, Arroyo, Juan J., Vasić, Marko, Lozić, Maja, Glumac, Sofija, Hoe, See Ziau, Hindmarch, Charles Colin Thomas, Murphy, David, Kiew, Lik Voon, Lee, Hong Boon, Vicent, Maria J., Chung, Lip Yong, Japundžić-Žigon, Nina, "Hemodynamic effects of HPMA copolymer based doxorubicin conjugate: A randomized controlled and comparative spectral study in conscious rats" in Nanotoxicology, 11, no. 2 (2017):210-222,
https://doi.org/10.1080/17435390.2017.1285071 . .

TY  - JOUR
AU  - Loncar-Turukalo, T.
AU  - Vasić, Marko
AU  - Tasić, T.
AU  - Mijatović, G.
AU  - Glumac, S.
AU  - Bajić, Dragana
AU  - Japunzic-Zigon, N.
PY  - 2015
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/813
AB  - The clinical use of doxorubicin, an effective chemotherapeutic is hampered by the development of irreversible cardiotoxicity. Here we test time-frequency analysis of heart rate (HR) variability (HRV) for early detection of doxorubicin-induced cardiotoxicity. Experiments were conducted in adult male Wistar rats treated for 15 days with doxorubicin (DOXO, total dose 15 mg kg(-1), i.p.) or saline (CONT). DOXO rats exhibited cardiotoxicity confirmed by histological examination without developing heart failure as estimated by echocardiography. However, HR variability increase reflected subtle microscopic changes of cardiac toxicity in DOXO rats. The results recommend time-frequency analysis of HRV for early detection of doxorubicin-induced cardiomyopathy.
PB  - IOP Publishing Ltd, Bristol
T2  - Physiological Measurement
T1  - Heart rate dynamics in doxorubicin-induced cardiomyopathy
EP  - 739
IS  - 4
SP  - 727
VL  - 36
DO  - 10.1088/0967-3334/36/4/727
ER  - 

@article{
author = "Loncar-Turukalo, T. and Vasić, Marko and Tasić, T. and Mijatović, G. and Glumac, S. and Bajić, Dragana and Japunzic-Zigon, N.",
year = "2015",
abstract = "The clinical use of doxorubicin, an effective chemotherapeutic is hampered by the development of irreversible cardiotoxicity. Here we test time-frequency analysis of heart rate (HR) variability (HRV) for early detection of doxorubicin-induced cardiotoxicity. Experiments were conducted in adult male Wistar rats treated for 15 days with doxorubicin (DOXO, total dose 15 mg kg(-1), i.p.) or saline (CONT). DOXO rats exhibited cardiotoxicity confirmed by histological examination without developing heart failure as estimated by echocardiography. However, HR variability increase reflected subtle microscopic changes of cardiac toxicity in DOXO rats. The results recommend time-frequency analysis of HRV for early detection of doxorubicin-induced cardiomyopathy.",
publisher = "IOP Publishing Ltd, Bristol",
journal = "Physiological Measurement",
title = "Heart rate dynamics in doxorubicin-induced cardiomyopathy",
pages = "739-727",
number = "4",
volume = "36",
doi = "10.1088/0967-3334/36/4/727"
}

Loncar-Turukalo, T., Vasić, M., Tasić, T., Mijatović, G., Glumac, S., Bajić, D.,& Japunzic-Zigon, N.. (2015). Heart rate dynamics in doxorubicin-induced cardiomyopathy. in Physiological Measurement
IOP Publishing Ltd, Bristol., 36(4), 727-739.
https://doi.org/10.1088/0967-3334/36/4/727

Loncar-Turukalo T, Vasić M, Tasić T, Mijatović G, Glumac S, Bajić D, Japunzic-Zigon N. Heart rate dynamics in doxorubicin-induced cardiomyopathy. in Physiological Measurement. 2015;36(4):727-739.
doi:10.1088/0967-3334/36/4/727 .

Loncar-Turukalo, T., Vasić, Marko, Tasić, T., Mijatović, G., Glumac, S., Bajić, Dragana, Japunzic-Zigon, N., "Heart rate dynamics in doxorubicin-induced cardiomyopathy" in Physiological Measurement, 36, no. 4 (2015):727-739,
https://doi.org/10.1088/0967-3334/36/4/727 . .