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Anthracycline-Dependent Cardiotoxicity and Extracellular Matrix RemodelingAnthracycline-Dependent Cardiotoxicity

Dragana Nikitovic, PhD; Ivo Juranek, MD, PhD; Martin F. Wilks, MD, PhD; Maria Tzardi, MD, PhD; Aristidis Tsatsakis, PhD; George N. Tzanakakis, MD, PhD
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From the Department of Anatomy-Histology-Embryology (Drs Nikitovic and Tzanakakis), the Department of Pathology (Dr Tzardi), and the Department of Forensic Sciences and Toxicology (Dr Tsatakis), School of Medicine, University of Crete, Heraklion, Greece; the Institute of Experimental Pharmacology and Toxicology (Dr Juranek), Slovak Academy of Sciences, Bratislava, Slovakia; and the Swiss Centre for Applied Human Toxicology (Dr Wilks), University of Basel, Basel, Switzerland.

CORRESPONDENCE TO: Dragana Nikitovic, PhD, Department of Anatomy-Histology-Embryology, School of Medicine, University of Crete, Voutes, Heraklion 71003, Greece; e-mail: dnikitovic@med.uoc.gr


Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details.


Chest. 2014;146(4):1123-1130. doi:10.1378/chest.14-0460
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The mechanisms of anthracycline-dependent cardiotoxicity have been studied widely, with the suggested principal mechanism of anthracycline damage being the generation of reactive oxygen species by iron-anthracycline complexes, leading to lipid peroxidation and membrane damage. An increasing number of researchers studying cardiovascular events associated with anthracycline-based chemotherapy are addressing cardiac extracellular matrix (ECM) remodeling. The heart is an efficient muscular pump, with the cardiomyocytes and intramural coronary vasculature of the heart tethered in an ECM consisting of a network of fibrillar, structural proteins, mostly collagens. Increasing evidence suggests that the ECM plays a complex and diverse role in the processes initiated by anthracycline-class drugs that lead to cardiac damage. This review discusses adverse myocardial remodeling induced by anthracyclines and focuses on their mechanisms of action.

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