Big ET-1 is a promising cardiotoxicity marker in childhood cancer survivors

Big ET-1 is a promising cardiotoxicity marker in childhood cancer survivors

Advancements in oncological therapies have resulted in a childhood cancer survivor (CCS) long-term survival rate exceeding 80%.  However, up to 60% of CCS are exposed to cardiotoxic treatments, significantly increasing their risk of congestive heart failure (CHF). CHF is a leading cause of long-term morbidity and mortality, with CCS facing a 15-fold higher incidence of CHF and a 7-fold greater risk of premature cardiac death compared to the general population (1).

Big Endothelin-1 (Big ET-1) is the inactive precursor of Endothelin-1 (ET-1), a 21-amino acid peptide that functions as one of the most potent vasoconstrictors in the human cardiovascular system. Under physiological conditions, Big ET-1 is cleaved by endothelin-converting enzyme (ECE) to generate active ET-1, which exerts its effects primarily through endothelin receptor type A (ETA) and type B (ETB) on vascular smooth muscle cells and endothelial cells (2).

Endothelial damage is characterized by dysfunction of the vascular endothelium, leading to increased permeability, pro-inflammatory and pro-thrombotic states, and impaired vasodilatory responses (3). Elevated circulating levels of Big ET-1 serve as a biomarker for endothelial cell activation and injury because increased production or impaired processing of Big ET-1 reflects endothelial cell distress (4). This dysfunction is a central mechanism in the pathogenesis of various cardiovascular diseases, including hypertension, atherosclerosis, and cardiomyopathy.

Big ET-1 is a promising cardiotoxicity marker in childhood cancer survivors

A recent study published in Cardiovascular Toxicology, investigated the long-term cardiotoxic effects of cancer therapy in CCS through a dual approach combining CMR imaging and blood biomarkers (5).

Big Endothelin-1 was measured in blood samples with an ELISA assay from BIOMEDICA.

 Big-ET-1 ELISA kit highlights (BI-20082H)

 – HIGH SENSITIVITY – direct measurement

– RELIABLE – Fully validated according to international guidelines

– Published cut-off values

– TRUSTED – widely cited in over 90 publications

 

 

Big ET-1 is a stable marker for investigating endothelial damage in cardiovascular diseases.

Long-term Subclinical Cardiotoxicity of Modern Cardiotoxic Treatment Protocols in Childhood Cancer Survivors Assessed by Cardiovascular Magnetic Resonance T1 Mapping and Circulatory Biomarkers

Key Findings

• CMR imaging revealed differences between CCS and control subjects
• In CCS, biomarkers indicating endothelial activation (Big ET-1) and oxidative stress (MPO, IMA) were elevated
• Blood biomarkers can enhance early detection and risk assessment of myocardial abnormalities

 

Monitoring Big ET-1 alongside imaging may improve long-term cardiac outcomes in childhood cancer survivors.

Long-term Subclinical Cardiotoxicity of Modern Cardiotoxic Treatment Protocols in Childhood Cancer Survivors Assessed by Cardiovascular Magnetic Resonance T1 Mapping and Circulatory Biomarkers. Panovský R, Tomandlová M, Mojica-Pisciotti ML, Kepák T, Máchal J, Feitová V, Frič J, Hortová-Kohoutková M, Holeček T, Tomandl J, Opatřil L, Kincl V.Cardiovasc Toxicol. 2026 Jan 28;26(2):23. doi: 10.1007/s12012-026-10098-8. PMID: 41604073; PMCID: PMC12852242.

Abstract

Childhood cancer survivors (CCS) are at increased risk of developing heart disease due to the cardiotoxic effects of oncological treatment. This study aimed to investigate the long-term cardiotoxic effects of cancer therapy in CCS using a multimodal approach combining cardiac magnetic resonance (CMR) imaging and circulating blood biomarkers. A total of 117 CCS (mean age 24.7 ± 5.2 years), at least five years post-treatment and in complete remission, were prospectively enrolled. All participants underwent CMR, including T1 mapping, and blood analysis for biomarkers of endothelial damage and oxidative stress. Parameters were compared with sex- and age-matched healthy control groups. Anthracycline treatment was administered in 82.9% of CCS (mean cumulative doxorubicin equivalent dose 231.7 ± 92.0 mg/m²). Left ventricular ejection fraction and mitral annular plane systolic excursion were significantly reduced in CCS compared to controls (59.0 ± 5.5% vs. 67.2 ± 6.9%, p < 0.001; 12.5 ± 1.7 mm vs. 13.9 ± 2.2 mm, p = 0.001). Late gadolinium enhancement was detected in four CCS. No significant differences in global native T1 relaxation time or extracellular volume were observed. N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels remained within normal limits but correlated with native T1, ECV, and MAPSE. Levels of myeloperoxidase, big endothelin-1, and ischemia-modified albumin were significantly higher than in controls. Subclinical myocardial changes were detected in long-term CCS using CMR and circulating biomarkers. These findings support the utility of a multimodal approach for the early identification of individuals at increased cardiovascular risk after childhood cancer treatment.

 

Literature

1. Long-term Subclinical Cardiotoxicity of Modern Cardiotoxic Treatment Protocols in Childhood Cancer Survivors Assessed by Cardiovascular Magnetic Resonance T1 Mapping and Circulatory Biomarkers. Panovský R, Tomandlová M, Mojica-Pisciotti ML, Kepák T, Máchal J, Feitová V, Frič J, Hortová-Kohoutková M, Holeček T, Tomandl J, Opatřil L, Kincl V.Cardiovasc Toxicol. 2026 Jan 28;26(2):23. doi: 10.1007/s12012-026-10098-8. PMID: 41604073; PMCID: PMC12852242.
2. Endothelin and the Cardiovascular System: The Long Journey and Where We Are Going. Haryono A, Ramadhiani R, Ryanto GRT, Emoto N. Biology (Basel). 2022 May 16;11(5):759. doi: 10.3390/biology11050759. PMID: 35625487; PMCID: PMC9138590.
3. Endothelial Dysfunction, Inflammation and Coronary Artery Disease: Potential Biomarkers and Promising Therapeutical Approaches. Medina-Leyte DJ, Zepeda-García O, Domínguez-Pérez M, González-Garrido A, Villarreal-Molina T, Jacobo-Albavera L. Int J Mol Sci. 2021 Apr 8;22(8):3850. doi: 10.3390/ijms22083850. PMID: 33917744; PMCID: PMC8068178.
4. Plasma big endothelin-1 levels at admission and future cardiovascular outcomes: A cohort study in patients with stable coronary artery disease. Zhou BY, Guo YL, Wu NQ, Zhu CG, Gao Y, Qing P, Li XL, Wang Y, Dong Q, Liu G, Xu RX, Cui CJ, Sun J, Li JJ. Int J Cardiol. 2017 Mar 1;230:76-79. doi: 10.1016/j.ijcard.2016.12.082. Epub 2016 Dec 21. PMID: 28038820.
5. Long-term Subclinical Cardiotoxicity of Modern Cardiotoxic Treatment Protocols in Childhood Cancer Survivors Assessed by Cardiovascular Magnetic Resonance T1 Mapping and Circulatory Biomarkers. Panovský R, Tomandlová M, Mojica-Pisciotti ML, Kepák T, Máchal J, Feitová V, Frič J, Hortová-Kohoutková M, Holeček T, Tomandl J, Opatřil L, Kincl V. Cardiovasc Toxicol. 2026 Jan 28;26(2):23. doi: 10.1007/s12012-026-10098-8. PMID: 41604073; PMCID: PMC12852242.