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Subcutaneous B16 melanoma impairs intrinsic pressure generation and relaxation of the heart, which are not restored by short-term voluntary exercise in mice
University Of Turku, Turku, Finland.
University Of Turku, Turku, Finland.
University Of Turku, Turku, Finland; Poznan University Of Medical Sciences, Poznan, Poland.
University of Turku, Turku, Finland.
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2022 (English)In: American Journal of Physiology. Heart and Circulatory Physiology, ISSN 0363-6135, E-ISSN 1522-1539, Vol. 322, no 6, p. H1044-H1056Article in journal (Refereed) Published
Abstract [en]

The aim of this study was to investigate whether subcutaneous melanoma impairs intrinsic cardiac function and hypoxia tolerance in mice. In addition, it was investigated whether these changes could be prevented by voluntary wheel-running exercise. The roles of different molecular pathways were also analyzed. Male mice (C57Bl/6NCrl) were divided into unexercised tumor-free group, unexercised melanoma group, and exercised melanoma group. The experiment lasted 2.7 ± 0.1 wk (determined by the tumor size) after which the heart function was measured in different oxygen levels ex vivo using Langendorff method. All the melanoma mice had lower pressure amplitude (50.3%), rate of pressure production (54.1%), and decline (52.5%) in hearts ex vivo when compared with tumor-free group. There were no functional differences between the two melanoma groups. All the groups had similar weight changes, heart weights, cardiomyocyte sizes, levels of Ca2+ channels, energy metabolism enzyme activities, lipid peroxidation, and reactive oxygen species in their cardiac tissue homogenates. However, all the melanoma mice had 7.4% lower superoxidase dismutase activity compared with the control animals, which might reduce the ability of the heart to react to changes in oxidative stress. The exercising melanoma group had a 28.6% higher average heart capillary density compared with the unexercised melanoma group. Short-term wheel running did not affect the tumor growth. In conclusion, subcutaneous melanoma seems to impair intrinsic heart function even before cachexia, and these functional alterations were not caused by any of the measured molecular markers. Short-term voluntary wheel-running exercise was insufficient to alleviate the intrinsic cardiac impairments caused by melanoma.NEW & NOTEWORTHY Melanoma has been shown to induce cardiac atrophy and impair cardiac function in vivo, however, it has not been investigated how melanoma affects the intrinsic heart function. Here, we showed that subcutaneous melanoma can impair intrinsic heart function in noncachectic mice, decreasing the heart's pressure production and relaxation. In addition, we investigated whether short-term voluntary wheel-running exercise could attenuate the impairment of intrinsic cardiac function. However, our results do not seem to support this hypothesis. © 2022 the American Physiological Society.

Place, publisher, year, edition, pages
Rockville: American Physiological Society , 2022. Vol. 322, no 6, p. H1044-H1056
Keywords [en]
cancer, ex vivo, heart function, oxidative stress
National Category
Cardiac and Cardiovascular Systems
Identifiers
URN: urn:nbn:se:hh:diva-49082DOI: 10.1152/ajpheart.00586.2021ISI: 000803834700002PubMedID: 35486476Scopus ID: 2-s2.0-85131018177OAI: oai:DiVA.org:hh-49082DiVA, id: diva2:1724980
Funder
Academy of Finland, 324243
Note

Funding text: The study was funded by the Turku Collegium of Science, the Kone Foundation, and Medicine and the Academy of Finland Grant 324243.

Available from: 2023-01-09 Created: 2023-01-09 Last updated: 2023-01-09Bibliographically approved

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