Compromised Endothelial Regeneration as a Potential Contributor to Long-Term Cardiovascular Complications in Childhood Cancer Survivors
5 affiliations
- 1Department of Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119228, Singapore
- 2Cardiovascular Research Institute, Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, National University Health System, Singapore 119228, Singapore
- 3Royal College of Surgeons in Ireland (Medicine), School of Medicine, Royal College of Surgeons in Ireland, D02 YN77 Dublin, Ireland
- 4Cardiovascular Disease Translational Research Programme, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119228, Singapore
- 5Division of Cardiology, Department of Paediatrics, Khoo Teck Puat–National University Children’s Medical Institute, National University Health System, Singapore 119228, Singapore
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.
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BibTeX
@article{markandran2026compromised,
title = {{Compromised Endothelial Regeneration as a Potential Contributor to Long-Term Cardiovascular Complications in Childhood Cancer Survivors}},
author = {Kasturi Markandran and Tricia Jingwen Ng and Elena Tan and Czaryna Kaye Mendoza Clemente and Rina Miao Qin Wang and Yee Phong Lim and Karan Attal and Kristine Nicole Mendoza Clemente and Hammresh S and Sik Yin Roger Foo and Ching Kit Chen},
journal = {Cells},
year = {2026},
month = nov,
doi = {10.3390/cells15212040},
url = {https://www.mdpi.com/2073-4409/15/21/2040},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Compromised Endothelial Regeneration as a Potential Contributor to Long-Term Cardiovascular Complications in Childhood Cancer Survivors
AU - Kasturi Markandran
AU - Tricia Jingwen Ng
AU - Elena Tan
AU - Czaryna Kaye Mendoza Clemente
AU - Rina Miao Qin Wang
AU - Yee Phong Lim
AU - Karan Attal
AU - Kristine Nicole Mendoza Clemente
AU - Hammresh S
AU - Sik Yin Roger Foo
AU - Ching Kit Chen
PY - 2026
DA - 2026/11/09
JO - Cells
DO - 10.3390/cells15212040
UR - https://www.mdpi.com/2073-4409/15/21/2040
AB - 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.
SN - 2073-4409
ER -