Cardiovascular variability and beta-ARs gene expression at two stages of doxorubicin - Induced cardiomyopathy
Само за регистроване кориснике
2019
Аутори
Vasić, MarkoLoncar-Turukalo, Tatjana
Tasić, Tatjana
Matić, Marija
Glumac, Sofija
Bajić, Dragana
Popović, Branka
Japundžić-Žigon, Nina
Чланак у часопису (Објављена верзија)
Метаподаци
Приказ свих података о документуАпстракт
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 lowe...r 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.
Кључне речи:
Doxorubicin / Cardiotoxicity / beta-adrenergic receptors / Heart rate variability / Blood pressure variabilityИзвор:
Toxicology & Applied Pharmacology, 2019, 362, 43-51Издавач:
- Academic Press Inc Elsevier Science, San Diego
Финансирање / пројекти:
- Функционална геномика хипоталамуса и медуле у хипертензији индукованој хроничним стресом (RS-41013)
- Развој мултиваријабилних метода за аналитичку подршку биомедицинској дијагностици (RS-32040)
DOI: 10.1016/j.taap.2018.10.015
ISSN: 0041-008X
PubMed: 30342983
WoS: 000455971700006
Scopus: 2-s2.0-85055260788
Колекције
Институција/група
Stomatološki fakultetTY - 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://smile.stomf.bg.ac.rs/handle/123456789/2469 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 & Applied Pharmacology T1 - Cardiovascular variability and beta-ARs gene expression at two stages of doxorubicin - Induced cardiomyopathy VL - 362 SP - 43 EP - 51 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 & Applied Pharmacology", title = "Cardiovascular variability and beta-ARs gene expression at two stages of doxorubicin - Induced cardiomyopathy", volume = "362", pages = "43-51", 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 & 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 & 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 & Applied Pharmacology, 362 (2019):43-51, https://doi.org/10.1016/j.taap.2018.10.015 . .