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Compromised Endothelial Regeneration as a Potential Contributor to Long-Term Cardiovascular Complications in Childhood Cancer Survivors

Year: 2026

Type: article

Abstract: Anthracyclines are central to childhood cancer therapy but predispose patients to cardiovascular toxicity and long-term cardiovascular risk. Endothelial injury and impaired repair contribute to this, yet paediatric data remain limited. This study longitudinally assessed endothelial injury and repair by quantifying circulating endothelial cells (CECs) and endothelial progenitor cells (EPCs). In a single-centre prospective cohort, children (<18 years) with leukaemia (n = 35) or lymphoma (n = 13) were studied at four timepoints: pre-treatment (Pre), ~1 month post-treatment (End), 3 months (3M), and 1 year (1Y). Blood mononuclear cells were analysed by flow cytometry to quantify CECs and EPCs, and EPC fate by p16 (senescence) and Annexin V (apoptosis). Cardiac biomarkers and left ventricular function were assessed. Longitudinal trends of CEC and EPC counts were similar between leukaemia and lymphoma participants. CECs were highest at pre-treatment and declined significantly thereafter, though they remained marginally elevated during remission compared with healthy controls, indicating endothelial damage had largely subsided following treatment. EPCs were highest at pre-treatment and decreased below healthy controls during remission, suggesting impaired baseline endothelial maintenance and repair. While EPC fate did not alter significantly from healthy controls before and after treatment in leukaemia patients, in lymphoma patients the EPCs were pre-dominantly senescent right after treatment completion and apoptotic activity gradually returned to healthy control levels, suggesting reduced EPC involvement in tumour-associated angiogenesis following treatment and persistent impairment of endothelial regenerative capacity, although their relative contributions cannot be determined from the present study. In summary, this study demonstrates that endothelial injury largely subsides following treatment, but regeneration, and hence repair, remains impaired during remission.

Source: Cells

DOI: 10.3390/cells15212040