S2581
Radiobiology – Normal tissue radiobiology
ESTRO 2026
vascular remodeling, characterized by endothelial dysfunction, neointima formation, and smooth muscle cell hyperplasia highly resembles the pathological features of pulmonary hypertension (PH). However, the intercellular mechanisms that drive this remain unclear, hindering the development of effective intervention strategies. This study aimed to establish an in vitro model to investigate the mechanisms of radiation-induced vascular remodeling.
Material/Methods: To investigate cell- cell communication in vascular remodeling,
we established an in vitro medium transfer model using irradiated endothelial cells (IR-ECs) to produce conditioned medium (CM). Subsequently, this medium was administered to vascular smooth muscle cells (VSMCs). EDU incorporation and scratch assay were performed to detect changes in proliferation and migration of SMCs, respectively. Additionally, transcriptomic sequencing of both IR-ECs and CM- treated VSMCs was executed to elucidate the regulatory pathways underlying behavioral changes of VSMCs. Results: Conditioned medium from IR-ECs stimulated VSMC proliferation and migration in a dose-dependent manner, as indicated by increased cell numbers (Fig.1) and accelerated wound closure. Furthermore, treatment with 8Gy conditioned medium (CM8) resulted in a 1.3-fold increase in EdU ⁺ VSMC number. In a separate experiment, this response persisted even after VSMCs were irradiated, suggesting sustained paracrine signaling. Transcriptomic profiling of IR-ECs revealed increased interferon- α a/ γ signaling, activation of the IL6–JAK–STAT3 pathway, and metabolic reprogramming toward glycolysis. CM from these IR-ECs induced a phenotype switch in VSMCs (Fig.2). Pathway analysis showed enrichment of Interleukin-6 and Leukemia Inhibitory Factor signaling pathways. This suggests that inflammatory cytokines contribute to radiation-induced vascular remodeling, which also observed in PH. However, classical PH related pathways—endothelin, nitric oxide, and prostacyclin—were not significantly upregulated in our data, implying distinct molecular mechanisms of radiation-induced vascular damage as compared with PH.
Conclusion: To investigate the interactions between irradiated endothelial cells and vascular smooth muscle cells, an in vitro model was established. In this model VSMCs exhibited key features of pulmonary hypertension. Inflammatory cytokines appear to play a critical role in radiation-induced vascular remodeling. Although there is partial overlap with the mechanisms underlying PH, the signaling pathways involved in radiation-induced vascular changes are not entirely identical. Deeper insight into these pathways may uncover new therapeutic strategies to prevent or mitigate radiation- induced cardiopulmonary toxicity. References: 1. Ghobadi, G., et al., Lung irradiation induces pulmonary vascular remodeling resembling pulmonary arterial hypertension. Thorax, 2012. 67(4): p. 334-41. Keywords: radiation, inflammation, vascular remodeling FLASH Helium irradiation mitigates radiation- induced lung fibrosis while preserving tumor control in preclinical mouse models Mahdi Akbarpour 1,2 , Ivana Dokic 1,2 , Max Knoll 1,2 , Saleh Eskandarian 1,2 , Nora Schumacher 1,2 , Claudia Rittmüller 1,2 , Stephan Brons 3 , Jürgen Debus 1,2 , Amir Abdollahi 1,2 , Mahmoud Moustafa 1,2 1 Clinical Cooperation Unit Translational Radiation Oncology, German Cancer Research Center (DKFZ), Heidelberg, Germany. 2 Molecular and Translational Radiation Oncology, Medical Faculty Heidelberg University (MFHD), Heidelberg, Germany. 3 Medical Physics, Heidelberg Ion Beam Therapy Center (HIT), Heidelberg, Germany Purpose/Objective: Radiation-induced lung fibrosis (RILF) remains a major dose-limiting toxicity in thoracic cancer radiotherapy. Ultra-high dose rate electron irradiation (FLASH) has shown potential to spare normal tissue while Proffered Paper 4020
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