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

English version

Autoři: Julie Birkmose Axelsen ^aff001; Stine Andersen ^aff001; Xiao-Qing Sun ^aff002; Steffen Ringgaard ^aff003; Janus Adler Hyldebrandt ^aff004; Kondababu Kurakula ^aff005; Marie-José Goumans ^aff005; Frances S. de Man ^aff002; Jens Erik Nielsen-Kudsk ^aff001; Harm-Jan Bogaard ^aff002; Asger Andersen ^aff001
Působiště autorů: Department of Cardiology–Research, Aarhus University Hospital, Aarhus, Denmark ^aff001; Department of Pulmonology, VU University Medical Center, Amsterdam, The Netherlands ^aff002; MR Centre, Aarhus University Hospital, Aarhus, Denmark ^aff003; Department of Anesthesiology and Intensive Care, Aarhus University Hospital, Aarhus, Denmark ^aff004; Department of Cell and Chemical Biology, Leiden University Medical Center, Leiden, The Netherlands ^aff005
Vyšlo v časopise: PLoS ONE 14(11)
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pone.0225122

Souhrn

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.

Klíčová slova:

Gene expression – Inflammation – Collagens – Fibrosis – Surgical and invasive medical procedures – Protein expression – Pulmonary hypertension – Cardiac ventricles

Zdroje

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