Synthetic preimplantation factor ameliorates the severity of radiotherapy-induced heart disease in a rat model
16 affiliations
- 1Department of Biochemistry and Interdisciplinary Center of Excellence, Albert Szent-Györgyi Medical School, University of Szeged
- 2Center for Biomedical Research and Translational Surgery, Medical University of Vienna
- 3Department of Oncotherapy, Albert Szent-Györgyi Medical School, University of Szeged
- 4Department of Pathophysiology, Albert Szent-Györgyi Medical School, University of Szeged
- 5Institute of Pharmacodynamics and Biopharmacy, University of Szeged
- 6Metabolic and Newborn Screening Laboratory, Department of Pediatrics, Albert Szent-Györgyi Medical School, University of Szeged
- 7Center for Anatomy and Cell Biology, Medical University of Vienna
- 8Department of Pathology, Albert Szent-Györgyi Medical School, University of Szeged
- 9Synthetic and Systems Biology Unit, HUN-REN Biological Research Centre
- 10Single-Cell Technologies Ltd
- 11Institute for Molecular Medicine Finland (FIMM), University of Helsinki
- 12Institute of AI for Health, Helmholtz Zentrum München
- 13S.I.E.P. The Society for the Investigation of Early Pregnancy
- 14Obstetrics, Gynecology & Reproductive Sciences, Miller School of Medicine, University of Miami
- 15BioIncept, LLC (*sPIF Proprietary)
- 16Faculty of Health and Social Sciences, Gál Ferenc University
Abstract
Background: Radiation-induced heart disease (RIHD) is a potential side effect of radiotherapy (RT) for thoracic tumors and breast cancers, often causing diastolic dysfunction, left ventricular hypertrophy (LVH), and fibrosis. Preimplantation factor (PIF), an embryonic immunomodulatory peptide, has shown protective effects against acute radiation syndrome. We investigated whether synthetic PIF (sPIF) could mitigate RIHD development in rats and tumor cell proliferation in human breast cancer cell lines.
Methods: Adult male Sprague-Dawley rats were allocated into three experimental groups: vehicle-treated control, vehicle-treated RT (50 Gy, focused on the heart), and RT treated with sPIF, monitored at 1, 3, and 15 weeks. Endpoint assessments included transthoracic echocardiography, histopathology, qPCR, Western blotting, and UHPLC–MS/MS in the left ventricular (LV) samples. The effects of sPIF on hypertrophy, fibrosis, and proliferation were investigated in H9c2 cardiomyoblasts, human ventricular cardiac fibroblasts (HVCFs), and human breast carcinoma cells, respectively.
Results: sPIF decreased LV expression of inflammatory markers at week 3 and attenuated RT-induced LVH and fibrosis, with reduced nitrotyrosine accumulation at week 15. sPIF suppressed angiotensin II–induced hypertrophy in H9c2 cells, inhibited transforming growth factor- β 1 (TGF β 1)–induced collagen-1 expression in HVCFs, and enhanced the anti-proliferative response to RT in human breast carcinoma cells.
Conclusions: These findings suggest the potential of sPIF as a cardioprotective agent for the management of RIHD and warrant further mechanistic investigations.
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BibTeX
@article{kovacs2026synthetic,
title = {{Synthetic preimplantation factor ameliorates the severity of radiotherapy-induced heart disease in a rat model}},
author = {Mónika Gabriella Kovács and Ana Isabel Antunes Goncalves and Zoltán Varga and Réka Losonczi and Klaudia Kupecz and Dávid Volford and Szonja Polett Pósa and Renáta Minorics and Zsolt Galla and Karin Zins and Anita Sejben and András Kriston and Ferenc Kovács and Péter Horváth and Péter Monostori and Gábor Cserni and István Zupkó and Bruno K. Podesser and Eytan R. Barnea and Zsuzsanna Kahán and Attila Kiss and Peter Pokreisz and Márta Sárközy},
journal = {Frontiers in Cardiovascular Medicine},
year = {2026},
month = oct,
doi = {10.3389/fcvm.2026.1946843},
url = {https://www.frontiersin.org/articles/10.3389/fcvm.2026.1946843/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Synthetic preimplantation factor ameliorates the severity of radiotherapy-induced heart disease in a rat model
AU - Mónika Gabriella Kovács
AU - Ana Isabel Antunes Goncalves
AU - Zoltán Varga
AU - Réka Losonczi
AU - Klaudia Kupecz
AU - Dávid Volford
AU - Szonja Polett Pósa
AU - Renáta Minorics
AU - Zsolt Galla
AU - Karin Zins
AU - Anita Sejben
AU - András Kriston
AU - Ferenc Kovács
AU - Péter Horváth
AU - Péter Monostori
AU - Gábor Cserni
AU - István Zupkó
AU - Bruno K. Podesser
AU - Eytan R. Barnea
AU - Zsuzsanna Kahán
AU - Attila Kiss
AU - Peter Pokreisz
AU - Márta Sárközy
PY - 2026
DA - 2026/10/16
JO - Frontiers in Cardiovascular Medicine
DO - 10.3389/fcvm.2026.1946843
UR - https://www.frontiersin.org/articles/10.3389/fcvm.2026.1946843/full
AB - Background: Radiation-induced heart disease (RIHD) is a potential side effect of radiotherapy (RT) for thoracic tumors and breast cancers, often causing diastolic dysfunction, left ventricular hypertrophy (LVH), and fibrosis. Preimplantation factor (PIF), an embryonic immunomodulatory peptide, has shown protective effects against acute radiation syndrome. We investigated whether synthetic PIF (sPIF) could mitigate RIHD development in rats and tumor cell proliferation in human breast cancer cell lines. Methods: Adult male Sprague-Dawley rats were allocated into three experimental groups: vehicle-treated control, vehicle-treated RT (50 Gy, focused on the heart), and RT treated with sPIF, monitored at 1, 3, and 15 weeks. Endpoint assessments included transthoracic echocardiography, histopathology, qPCR, Western blotting, and UHPLC–MS/MS in the left ventricular (LV) samples. The effects of sPIF on hypertrophy, fibrosis, and proliferation were investigated in H9c2 cardiomyoblasts, human ventricular cardiac fibroblasts (HVCFs), and human breast carcinoma cells, respectively. Results: sPIF decreased LV expression of inflammatory markers at week 3 and attenuated RT-induced LVH and fibrosis, with reduced nitrotyrosine accumulation at week 15. sPIF suppressed angiotensin II–induced hypertrophy in H9c2 cells, inhibited transforming growth factor- β 1 (TGF β 1)–induced collagen-1 expression in HVCFs, and enhanced the anti-proliferative response to RT in human breast carcinoma cells. Conclusions: These findings suggest the potential of sPIF as a cardioprotective agent for the management of RIHD and warrant further mechanistic investigations.
SN - 2297-055X
ER -