Key result
Inflammatory cytokines disrupt cardiomyocyte structure in vitro and impair ventricular systolic function in cancer models.
Why the study?
Cardiac dysfunction in cancer patients limits chemotherapy and survival, and the effects of inflammatory cytokines on cardiomyocyte mitochondria and cytoskeleton are not fully understood.
Systemic inflammation associated with cancer growth induces mitochondrial and cytoskeletal alterations in cardiomyocytes, potentially causing remote cardiac injury and impaired systolic function.
Answers are grounded in this paper and cite their sources.
Cancer-associated cytokines may impair cardiomyocyte mitochondria and contractility; leaves open whether anti-inflammatory strategies preserve systolic function in patients.
Cardiac dysfunction is often observed in patients with cancer also representing a serious problem limiting chemotherapeutic intervention and even patient survival. In view of the recently established role of the immune system in the control of cancer growth, the present work has been undertaken to investigate the effects of a panel of the most important inflammatory cytokines on the integrity and function of mitochondria, as well as of the cytoskeleton, two key elements in the functioning of cardiomyocytes. Either mitochondria features or actomyosin cytoskeleton organization of in vitro-cultured cardiomyocytes treated with different inflammatory cytokines were analyzed. In addition, to investigate the interplay between tumor growth and cardiac function in an in vivo system, immunocompetent female mice were inoculated with cancer cells and treated with the chemotherapeutic drug doxorubicin at a dosing schedule able to suppress tumor growth without inducing cardiac alterations. Analyses carried out in cardiomyocytes treated with the inflammatory cytokines, such as tumor necrosis factor α (TNF-α), interferon γ (IFN-γ), interleukin 6 (IL-6), IL-8, and IL-1β revealed severe phenotypic changes, for example, of contractile cytoskeletal elements, mitochondrial membrane potential, mitochondrial reactive oxygen species production and mitochondria network organization. Accordingly, in immunocompetent mice, the tumor growth was accompanied by increased levels of the inflammatory cytokines TNF-α, IFN-γ, IL-6, and IL-8, either in serum or in the heart tissue, together with a significant reduction of ventricular systolic function. The alterations of mitochondria and of microfilament system of cardiomyocytes, due to the systemic inflammation associated with cancer growth, could be responsible for remote cardiac injury and impairment of systolic function observed in vivo.
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Buoncervello et al. (2019) studied Cancer-associated cardiac dysfunction. Inflammatory cytokines (TNF-α, IFN-γ, IL-6, IL-8, IL-1β) and cancer growth was evaluated on Mitochondria features, actomyosin cytoskeleton organization, and ventricular systolic function. Exposure to inflammatory cytokines induced severe phenotypic changes in cardiomyocytes in vitro and was associated with reduced ventricular systolic function in a mouse model of cancer growth.
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