Initial Phase of Anthracycline Cardiotoxicity Involves Cardiac Fibroblasts Activation and Metabolic Switch.

Autor: Telesca M; Department of Experimental Medicine, University of Campania 'Luigi Vanvitelli', Via Costantinopoli 16, 80138 Naples, Italy., Donniacuo M; Department of Experimental Medicine, University of Campania 'Luigi Vanvitelli', Via Costantinopoli 16, 80138 Naples, Italy., Bellocchio G; Department of Experimental Medicine, University of Campania 'Luigi Vanvitelli', Via Costantinopoli 16, 80138 Naples, Italy., Riemma MA; Department of Experimental Medicine, University of Campania 'Luigi Vanvitelli', Via Costantinopoli 16, 80138 Naples, Italy., Mele E; Department of Experimental Medicine, University of Campania 'Luigi Vanvitelli', Via Costantinopoli 16, 80138 Naples, Italy., Dell'Aversana C; Department of Precision Medicine, University of Campania 'Luigi Vanvitelli', Via Costantinopoli 16, 80138 Naples, Italy.; BIOGEM, Via Camporeale, 83031 Ariano Irpino, Italy., Sgueglia G; Department of Precision Medicine, University of Campania 'Luigi Vanvitelli', Via Costantinopoli 16, 80138 Naples, Italy., Cianflone E; Department of Medical and Surgical Sciences, Magna Graecia University, Viale Europa, 88100 Catanzaro, Italy., Cappetta D; Department of Biological and Environmental Sciences and Technologies, University of Salento, Via Lecce-Monteroni, 73047 Lecce, Italy., Torella D; Department of Experimental and Clinical Medicine, Magna Graecia University, 88100 Catanzaro, Italy., Altucci L; Department of Precision Medicine, University of Campania 'Luigi Vanvitelli', Via Costantinopoli 16, 80138 Naples, Italy.; BIOGEM, Via Camporeale, 83031 Ariano Irpino, Italy.; Institute of Experimental Endocrinology and Oncology 'Gaetano Salvatore' (IEOS)-National Research Council (CNR), 80131 Naples, Italy., Castaldo G; Department of Molecular Medicine and Medical Biotechnologies, University of Naples 'Federico II', Via A. Pansini 5, 80131 Naples, Italy.; CEINGE-Advanced Biotechnologies 'Franco Salvatore', Via G. Salvatore 486, 80131 Naples, Italy., Rossi F; Department of Experimental Medicine, University of Campania 'Luigi Vanvitelli', Via Costantinopoli 16, 80138 Naples, Italy., Berrino L; Department of Experimental Medicine, University of Campania 'Luigi Vanvitelli', Via Costantinopoli 16, 80138 Naples, Italy., Urbanek K; Department of Molecular Medicine and Medical Biotechnologies, University of Naples 'Federico II', Via A. Pansini 5, 80131 Naples, Italy.; CEINGE-Advanced Biotechnologies 'Franco Salvatore', Via G. Salvatore 486, 80131 Naples, Italy., De Angelis A; Department of Experimental Medicine, University of Campania 'Luigi Vanvitelli', Via Costantinopoli 16, 80138 Naples, Italy.
Jazyk: angličtina
Zdroj: Cancers [Cancers (Basel)] 2023 Dec 21; Vol. 16 (1). Date of Electronic Publication: 2023 Dec 21.
DOI: 10.3390/cancers16010053
Abstrakt: The application of doxorubicin (DOX) is hampered by cardiotoxicity, with diastolic dysfunction as the earliest manifestation. Fibrosis leads to impaired relaxation, but the mechanisms that operate shortly after DOX exposure are not clear. We asked whether the activation of cardiac fibroblasts (CFs) anticipates myocardial dysfunction and evaluated the effects of DOX on CF metabolism. CFs were isolated from the hearts of rats after the first injection of DOX. In another experiment, CFs were exposed to DOX in vitro. Cell phenotype and metabolism were determined. Early effects of DOX consisted of diastolic dysfunction and unchanged ejection fraction. Markers of pro-fibrotic remodeling and evidence of CF transformation were present immediately after treatment completion. Oxygen consumption rate and extracellular acidification revealed an increased metabolic activity of CFs and a switch to glycolytic energy production. These effects were consistent in CFs isolated from the hearts of DOX-treated animals and in naïve CFs exposed to DOX in vitro. The metabolic switch was paralleled with the phenotype change of CFs that upregulated markers of myofibroblast differentiation and the activation of pro-fibrotic signaling. In conclusion, the metabolic switch and activation of CFs anticipate DOX-induced damage and represent a novel target in the early phase of anthracycline cardiomyopathy.
Databáze: MEDLINE
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