Anthracycline chemotherapy‐mediated vascular dysfunction as a model of accelerated vascular aging
Open Access
- 22 June 2021
- journal article
- Published by Wiley in Aging and Cancer
- Vol. 2 (1-2), 45-69
- https://doi.org/10.1002/aac2.12033
Abstract
Cardiovascular diseases (CVD) are the leading cause of death worldwide, and age is by far the greatest risk factor for developing CVD. Vascular dysfunction, including endothelial dysfunction and arterial stiffening, is responsible for much of the increase in CVD risk with aging. A key mechanism involved in vascular dysfunction with aging is oxidative stress, which reduces the bioavailability of nitric oxide (NO) and induces adverse changes to the extracellular matrix of the arterial wall (e.g., elastin fragmentation/degradation, collagen deposition) and an increase in advanced glycation end products, which form crosslinks in arterial wall structural proteins. Although vascular dysfunction and CVD are most prevalent in older adults, several conditions can "accelerate" these events at any age. One such factor is chemotherapy with anthracyclines, such as doxorubicin (DOXO), to combat common forms of cancer. Children, adolescents and young adults treated with these chemotherapeutic agents demonstrate impaired vascular function and an increased risk of future CVD development compared with healthy age-matched controls. Anthracycline treatment also worsens vascular dysfunction in mid-life (50-64 years of age) and older (65 and older) adults such that endothelial dysfunction and arterial stiffness are greater compared to age-matched controls. Collectively, these observations indicate that use of anthracycline chemotherapeutic agents induce a vascular aging-like phenotype and that the latter contributes to premature CVD in cancer survivors exposed to these agents. Here, we review the existing literature supporting these ideas, discuss potential mechanisms as well as interventions that may protect arteries from these adverse effects, identify research gaps and make recommendations for future research.Keywords
This publication has 147 references indexed in Scilit:
- The Hallmarks of AgingCell, 2013
- Vascular endothelial dysfunction after anthracyclines treatment in children with acute lymphoblastic leukemiaKorean Journal of Pediatrics, 2013
- Sustained activation of AMPK ameliorates age-associated vascular endothelial dysfunction via a nitric oxide-independent mechanismMechanisms of Ageing and Development, 2012
- Doxorubicin pathwaysPharmacogenetics and Genomics, 2011
- Mitochondrial reactive oxygen species drive proinflammatory cytokine productionThe Journal of Experimental Medicine, 2011
- Aging and vascular endothelial function in humansClinical Science, 2011
- Mitochondria and aging in the vascular systemJournal of Molecular Medicine, 2010
- Short‐term calorie restriction reverses vascular endothelial dysfunction in old mice by increasing nitric oxide and reducing oxidative stressAging Cell, 2010
- Rapamycin fed late in life extends lifespan in genetically heterogeneous miceNature, 2009
- Nutrient-Sensitive Mitochondrial NAD+ Levels Dictate Cell SurvivalCell, 2007