Overwhelming data indicate that cancer survivors are at higher risk of cardiovascular diseases because chemotherapy induces cardiotoxicity. Mechanistic explanation of this phenomenon is necessary to advise the clinical practice on the prevention of cardiotoxicity in cancer patients. Here we propose that chemotherapy induces cardiotoxicity by inadvertently interrupting the homeostasis of cardiac stem cells and depleting the resident cardiac stem cells pool. As a result, the heart loses the capability of regeneration and repair and demonstrates the cardiotoxicity symptoms. Our hypothesis is supported by several lines of emerging evidence: the high incidence of cardiotoxicity in paediatric cancer patients who still have more cardiac stem cells in the myocardium; the rescue of anthracycline cardiomyopathy by injection of cardiac stem cells; and the adverse cardiotoxicity induced by inhibitors of oncogenic kinases or pathways which target cardiac stem cells besides cancer cells. This may promote our growing appreciation that cardiac stem cells represent new targets of chemotherapy that contribute to cardiotoxicity and open up novel strategies for the preservation or expansion of the cardiac stem cells pool to overcome cardiotoxicity associated with chemotherapy.
Background: Previous studies demonstrate that macrophages synthesis and release catecholamines, which regulate the immune responses in an autocrine manner. These responses are mediated in part by β-adrenoceptors expressed on macrophages. Some β-adrenoceptor antagonists are commonly used in clinical conditions. Here we investigated whether the chronic administration of β-adrenoceptor antagonists upregulate adrenergic system of alveolar macrophage and the potential mechanims. Methods: Propranolol (30 mg/kg·d) or atenolol (5 mg/kg·d) was administered by gavage to rats for 4 weeks. Then alveolar macrophages were isolated and the expression of β 1 or β 2 -adrenoceptor was detected by flow cytometric analysis. Dopamine β-hydroxylase expression was assessed by Western blot assay and the concentrations of noradrenaline, IL-6, and TNF-α in cell supernatants were measured using ELISA after 2 h or 24 h exposure of alveolar macrophages to 100 ng/ml lipopolysaccharide (LPS). Results: Propranolol increased the mean fluorescence intensity (MFI) of β 1 , β 2 -adrenoceptor and the frequency of β 1 -,β 2 -adrenoceptor positive macrophages. However, only the MFI of β 1 -adrenoceptor and the frequency of β 1 -adrenoceptor positive macrophages were increased by atenolol. Furthermore, both propranolol and atenolol promoted LPS-mediated dopamine β-hydroxylase protein expression and increased noradrenaline production in rat alveolar macrophages. This was accompanied by increased LPS-mediated IL-6 and TNF-α production in cell supernatants of alveolar macrophages. Conclusion: These findings demonstrate that propranolol or atenolol upregulates alveolar macrophage adrenergic system, and the response may be β 1 -adrenergic receptor subtype dependent.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.