Synthetic preimplantation factor ameliorates the severity of radiotherapy-induced heart disease in a rat model

Kovács, Mónika Gabriella and Antunes Goncalves, Ana Isabel and Varga, Zoltán and Losonczi, Réka and Kupecz, Klaudia and Volford, Dávid and Pósa, Szonja Polett and Minorics, Renáta and Galla, Zsolt and Zins, Karin and Sejben, Anita and Kriston, András and Kovács, Ferenc and Horváth, Péter and Monostori, Péter and Cserni, Gábor and Zupkó, István and Podesser, Bruno K. and Barnea, Eytan R. and Kahán, Zsuzsanna and Kiss, Attila and Pokreisz, Peter and Sárközy, Márta (2026) Synthetic preimplantation factor ameliorates the severity of radiotherapy-induced heart disease in a rat model. FRONTIERS IN CARDIOVASCULAR MEDICINE, 13 (N/A). pp. 1-19. ISSN 2297-055X

Preview

Text fcvm-13-1946843.pdf - Published Version Available under License Creative Commons Attribution. Download (12MB) | Preview

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-β1 (TGFβ1)–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.

Actions (login required)

View Item