학술논문
A Mouse Model of Dilated Cardiomyopathy Produced by Isoproterenol Acute Exposure Followed by 5-Fluorouracil Administration.
Document Type
Academic Journal
Author
Salerno N; Department of Experimental and Clinical Medicine, Magna Graecia University, 88100 Catanzaro, Italy.; Scalise M; Department of Experimental and Clinical Medicine, Magna Graecia University, 88100 Catanzaro, Italy.; Marino F; Department of Experimental and Clinical Medicine, Magna Graecia University, 88100 Catanzaro, Italy.; Filardo A; Department of Medical and Surgical Sciences, Magna Graecia University, 88100 Catanzaro, Italy.; Chiefalo A; Department of Experimental and Clinical Medicine, Magna Graecia University, 88100 Catanzaro, Italy.; Panuccio G; Department of Medical and Surgical Sciences, Magna Graecia University, 88100 Catanzaro, Italy.; Torella M; Department of Experimental Medicine, University of Campania 'L. Vanvitelli', 80138 Naples, Italy.; De Angelis A; Department of Experimental Medicine, University of Campania 'L. Vanvitelli', 80138 Naples, Italy.; De Rosa S; Department of Medical and Surgical Sciences, Magna Graecia University, 88100 Catanzaro, Italy.; Ellison-Hughes GM; Centre for Human and Applied Physiological Sciences, School of Basic and Medical Biosciences, Faculty of Life Sciences & Medicine, King's College London, Guy's Campus, London SE1 1UL, UK.; Urbanek K; Department of Molecular Medicine and Medical Biotechnology, Federico II University, 88121 Naples, Italy.; Viglietto G; Department of Experimental and Clinical Medicine, Magna Graecia University, 88100 Catanzaro, Italy.; Torella D; Department of Experimental and Clinical Medicine, Magna Graecia University, 88100 Catanzaro, Italy.; Cianflone E; Department of Medical and Surgical Sciences, Magna Graecia University, 88100 Catanzaro, Italy.
Source
Publisher: MDPI AG Country of Publication: Switzerland NLM ID: 101651414 Publication Model: Electronic Cited Medium: Internet ISSN: 2308-3425 (Electronic) Linking ISSN: 23083425 NLM ISO Abbreviation: J Cardiovasc Dev Dis Subsets: PubMed not MEDLINE
Subject
Language
English
Abstract
Appropriate dilated cardiomyopathy (DCM) animal models are highly desirable considering the pathophysiological and clinical heterogeneity of DCM. Genetically modified mice are the most widely and intensively utilized research animals for DCM. However, to translate discoveries from basic science into new and personalized medical applications, research in non-genetically based DCM models remains a key issue. Here, we characterized a mouse model of non-ischemic DCM induced by a stepwise pharmacologic regime of Isoproterenol (ISO) high dose bolus followed by a low dose systemic injection of the chemotherapy agent, 5-Fluorouracil (5-FU). C57BL/6J mice were injected with ISO and, 3 days after, were randomly assigned to saline or 5-FU. Echocardiography and a strain analysis show that ISO + 5FU in mice induces progressive left ventricular (LV) dilation and reduced systolic function, along with diastolic dysfunction and a persistent global cardiac contractility depression through 56 days. While mice treated with ISO alone recover anatomically and functionally, ISO + 5-FU causes persistent cardiomyocyte death, ensuing in cardiomyocyte hypertrophy through 56 days. ISO + 5-FU-dependent damage was accompanied by significant myocardial disarray and fibrosis along with exaggerated oxidative stress, tissue inflammation and premature cell senescence accumulation. In conclusions, a combination of ISO + 5FU produces anatomical, histological and functional cardiac alterations typical of DCM, representing a widely available, affordable, and reproducible mouse model of this cardiomyopathy.