Endothelial Dysfunction in Childhood Cancer Survivors: A Narrative Review

Abstract

Assessment of endothelial dysfunction in cancer survivors may have a role in the early identification of non-communicable diseases and cardiovascular late effects. Oncological therapies may impair endothelial function. Therefore, in patients such as childhood cancer survivors who could benefit from early cardioprotective pharmacological interventions, it is essential to monitor endothelial function, even if the optimal methodology for investigating the multifaceted aspects of endothelial dysfunction is still under debate. Biochemical markers, as well as invasive and non-invasive tools with and without pharmacological stimuli have been studied. Human clinical studies that have examined lifestyle or cancer treatment protocols have yielded evidence showing the involvement of lipid and lipoprotein levels, glycemic control, blood pressure, adiposity, inflammation, and oxidative stress markers on the state of endothelial health and its role as an early indicator of cardiometabolic risk. However, with regards to pharmacological interventions, cautious interpretation of the result attained whilst monitoring the endothelial function is warranted due to methodological limitations and substantial heterogeneity of the results reported in the published studies. In this narrative review, an overview of evidence from human clinical trials examining the effects of cancer therapies on endothelial disease is provided together with a discussion of endothelial function assessment using the different non-invasive techniques available for researchers and clinicians, in recent years.

Left Ventricular-Arterial Coupling and Vascular Function in Childhood Cancer Survivors Exposed to Anthracycline Chemotherapy

“…Of importance, endothelial dysfunction has been suggested to participate in the pathogenesis of myocardial damage related to anthracycline therapy, possibly mediated by increased oxidative stress, decreased NO production and increase in NO inactivation [ 28 ]. Besides these solid basis, previous studies showed contrasting data on the effects of anthracycline therapy on vascular endothelial function, as assessed by FMD, probably because of differences in anthracycline doses administered, follow-up times and coexistence of traditional CV risk factors [ 31 , 32 , 33 , 34 , 35 ]. Our data demonstrated that, in this relatively small cohort, endothelial-dependent function appears normal in the years after treatment, suggesting an inherent endothelial plasticity after removal of the toxic perturbation.…”

B-Cell Activating Factor Increases Related to Adiposity, Insulin Resistance, and Endothelial Dysfunction in Overweight and Obese Subjects

“…Moreover, it has been reported that during acute [ 55 ] and chronic inflammation [ 56 ], shear forces and inflammatory molecules promote EC dysfunction, increasing vWF secretion into circulation which, upon contact with circulating platelets, can trigger thrombogenic processes [ 57 ]. In OB subjects, circulating vWF concentrations have been directly related to BMI, increasing with higher BMI of the study subjects [ 58 , 59 ].…”

Circulating Biomarkers for Monitoring Chemotherapy-Induced Cardiotoxicity in Children

“…Further, cardiotoxicity is more commonly observed in patients who previously received anthracycline-based chemotherapy or showing cardiac risk factors. Radiation also causes endothelial dysfunction, resulting in intravascular thrombosis, myocardial ischemia, and interstitial fibrosis [ 55 ].…”