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

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.