Effects of 6-mercaptopurine in pressure overload induced right heart failure

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Effects of 6-mercaptopurine in pressure overload induced right heart failure. / Axelsen, Julie Birkmose; Andersen, Stine; Sun, Xiao-Qing et al.

In: PLOS ONE, Vol. 14, No. 11, e0225122, 2019.

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

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Axelsen, JB, Andersen, S, Sun, X-Q, Ringgaard, S, Hyldebrandt, JA, Kurakula, K, Goumans, M-J, de Man, FS, Nielsen-Kudsk, JE, Bogaard, H-J & Andersen, A 2019, 'Effects of 6-mercaptopurine in pressure overload induced right heart failure', PLOS ONE, vol. 14, no. 11, e0225122. https://doi.org/10.1371/journal.pone.0225122

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Axelsen JB, Andersen S, Sun X-Q, Ringgaard S, Hyldebrandt JA, Kurakula K, Goumans M-J, de Man FS, Nielsen-Kudsk JE, Bogaard H-J, et al. 2019. Effects of 6-mercaptopurine in pressure overload induced right heart failure. PLOS ONE. 14(11):Article e0225122. https://doi.org/10.1371/journal.pone.0225122

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@article{65654f543e5b479a8323cb7e7ad98de0,
title = "Effects of 6-mercaptopurine in pressure overload induced right heart failure",
abstract = "BACKGROUND: Several antineoplastic drugs have been proposed as new compounds for pulmonary arterial hypertension treatment but many have cardiotoxic side effects. The chemotherapeutic agent 6-mercaptopurine may have an effect in treatment of pulmonary arterial hypertension but at the same time, its effects on the afterload adaption of the right ventricle is unpredictable due to interaction with multiple downstream signalling pathways in the cardiomyocytes. We investigated the direct cardiac effects of 6-mercaptopurine in rats with isolated right heart failure caused by pulmonary trunk banding (PTB).METHODS: Male Wistar rat weanlings (112±2 g) were randomized to sham operation (sham, n = 10) or PTB. The PTB animals were randomized to placebo (PTB-control, n = 10) and 6-mercaptopurine (7.5 mg/kg/day) groups with treatment start before the PTB procedure (PTB-prevention, n = 10) or two weeks after (PTB-reversal, n = 10). Right ventricular effects were evaluated by echocardiography, cardiac MRI, invasive pressure-volume measurements, and histological and molecular analyses.RESULTS: PTB increased right ventricular afterload and caused right ventricular hypertrophy and failure. 6-mercaptopurine did not improve right ventricular function nor reduce right ventricular remodelling in both prevention and reversal studies compared with placebo-treated rats.CONCLUSION: Treatment with 6-mercaptopurine did not have any beneficial or detrimental effects on right ventricular function or remodelling. Our data suggest that treatment of pulmonary arterial hypertension with 6-mercaptopurine is not harmful to the failing right ventricle.",
author = "Axelsen, {Julie Birkmose} and Stine Andersen and Xiao-Qing Sun and Steffen Ringgaard and Hyldebrandt, {Janus Adler} and Kondababu Kurakula and Marie-Jos{\'e} Goumans and {de Man}, {Frances S} and Nielsen-Kudsk, {Jens Erik} and Harm-Jan Bogaard and Asger Andersen",
year = "2019",
doi = "10.1371/journal.pone.0225122",
language = "English",
volume = "14",
journal = "P L o S One",
issn = "1932-6203",
publisher = "public library of science",
number = "11",

}

RIS

TY - JOUR

T1 - Effects of 6-mercaptopurine in pressure overload induced right heart failure

AU - Axelsen, Julie Birkmose

AU - Andersen, Stine

AU - Sun, Xiao-Qing

AU - Ringgaard, Steffen

AU - Hyldebrandt, Janus Adler

AU - Kurakula, Kondababu

AU - Goumans, Marie-José

AU - de Man, Frances S

AU - Nielsen-Kudsk, Jens Erik

AU - Bogaard, Harm-Jan

AU - Andersen, Asger

PY - 2019

Y1 - 2019

N2 - BACKGROUND: Several antineoplastic drugs have been proposed as new compounds for pulmonary arterial hypertension treatment but many have cardiotoxic side effects. The chemotherapeutic agent 6-mercaptopurine may have an effect in treatment of pulmonary arterial hypertension but at the same time, its effects on the afterload adaption of the right ventricle is unpredictable due to interaction with multiple downstream signalling pathways in the cardiomyocytes. We investigated the direct cardiac effects of 6-mercaptopurine in rats with isolated right heart failure caused by pulmonary trunk banding (PTB).METHODS: Male Wistar rat weanlings (112±2 g) were randomized to sham operation (sham, n = 10) or PTB. The PTB animals were randomized to placebo (PTB-control, n = 10) and 6-mercaptopurine (7.5 mg/kg/day) groups with treatment start before the PTB procedure (PTB-prevention, n = 10) or two weeks after (PTB-reversal, n = 10). Right ventricular effects were evaluated by echocardiography, cardiac MRI, invasive pressure-volume measurements, and histological and molecular analyses.RESULTS: PTB increased right ventricular afterload and caused right ventricular hypertrophy and failure. 6-mercaptopurine did not improve right ventricular function nor reduce right ventricular remodelling in both prevention and reversal studies compared with placebo-treated rats.CONCLUSION: Treatment with 6-mercaptopurine did not have any beneficial or detrimental effects on right ventricular function or remodelling. Our data suggest that treatment of pulmonary arterial hypertension with 6-mercaptopurine is not harmful to the failing right ventricle.

AB - BACKGROUND: Several antineoplastic drugs have been proposed as new compounds for pulmonary arterial hypertension treatment but many have cardiotoxic side effects. The chemotherapeutic agent 6-mercaptopurine may have an effect in treatment of pulmonary arterial hypertension but at the same time, its effects on the afterload adaption of the right ventricle is unpredictable due to interaction with multiple downstream signalling pathways in the cardiomyocytes. We investigated the direct cardiac effects of 6-mercaptopurine in rats with isolated right heart failure caused by pulmonary trunk banding (PTB).METHODS: Male Wistar rat weanlings (112±2 g) were randomized to sham operation (sham, n = 10) or PTB. The PTB animals were randomized to placebo (PTB-control, n = 10) and 6-mercaptopurine (7.5 mg/kg/day) groups with treatment start before the PTB procedure (PTB-prevention, n = 10) or two weeks after (PTB-reversal, n = 10). Right ventricular effects were evaluated by echocardiography, cardiac MRI, invasive pressure-volume measurements, and histological and molecular analyses.RESULTS: PTB increased right ventricular afterload and caused right ventricular hypertrophy and failure. 6-mercaptopurine did not improve right ventricular function nor reduce right ventricular remodelling in both prevention and reversal studies compared with placebo-treated rats.CONCLUSION: Treatment with 6-mercaptopurine did not have any beneficial or detrimental effects on right ventricular function or remodelling. Our data suggest that treatment of pulmonary arterial hypertension with 6-mercaptopurine is not harmful to the failing right ventricle.

U2 - 10.1371/journal.pone.0225122

DO - 10.1371/journal.pone.0225122

M3 - Journal article

C2 - 31714926

VL - 14

JO - P L o S One

JF - P L o S One

SN - 1932-6203

IS - 11

M1 - e0225122

ER -