Molecular mechanisms of anthracycline cardiovascular toxicity.
| Autor: | Narezkina A; Department of Medicine, Division of Cardiovascular Medicine, UCSD Cardiovascular Institute, University of California, San Diego, CA, U.S.A., Narayan HK; Department of Pediatrics, Division of Cardiology, University of California, San Diego, CA, U.S.A., Zemljic-Harpf AE; Department of Anesthesiology, Veterans Affairs San Diego Healthcare System, San Diego, CA, U.S.A.; Department of Anesthesiology, University of California San Diego, La Jolla, CA, U.S.A. |
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| Jazyk: | angličtina |
| Zdroj: | Clinical science (London, England : 1979) [Clin Sci (Lond)] 2021 May 28; Vol. 135 (10), pp. 1311-1332. |
| DOI: | 10.1042/CS20200301 |
| Abstrakt: | Anthracyclines are effective chemotherapeutic agents, commonly used in the treatment of a variety of hematologic malignancies and solid tumors. However, their use is associated with a significant risk of cardiovascular toxicities and may result in cardiomyopathy and heart failure. Cardiomyocyte toxicity occurs via multiple molecular mechanisms, including topoisomerase II-mediated DNA double-strand breaks and reactive oxygen species (ROS) formation via effects on the mitochondrial electron transport chain, NADPH oxidases (NOXs), and nitric oxide synthases (NOSs). Excess ROS may cause mitochondrial dysfunction, endoplasmic reticulum stress, calcium release, and DNA damage, which may result in cardiomyocyte dysfunction or cell death. These pathophysiologic mechanisms cause tissue-level manifestations, including characteristic histopathologic changes (myocyte vacuolization, myofibrillar loss, and cell death), atrophy and fibrosis, and organ-level manifestations including cardiac contractile dysfunction and vascular dysfunction. In addition, these mechanisms are relevant to current and emerging strategies to diagnose, prevent, and treat anthracycline-induced cardiomyopathy. This review details the established and emerging data regarding the molecular mechanisms of anthracycline-induced cardiovascular toxicity. (© 2021 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.) |
| Databáze: | MEDLINE |
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