Long-Term Effects of Radiation Therapy on Cerebral Microvessel Proteome: A Six Month Post-Exposure Analysis
Year: 2025
Type: article
Abstract: Background: studies of endothelial injury remain limited. Investigating the molecular and cellular pathways connecting RT, endothelial dysfunction, and cognitive impairment is vital for developing targeted interventions. This study examines proteomic changes in cerebral microvessels following RT. Methods: We conducted a comprehensive quantitative analysis comparing the proteome in cerebral microvessels from five control mice and five irradiated mice (12 Gy) 6 months after RT. Bioinformatics analyses included gene ontology (GO) enrichment, Mitocarta analysis, Ingenuity Pathway Analysis (IPA), and iPathwayGuide. Predictions from the analyses were validated by western blotting. Results: Our data identified significant dysregulation of 414 proteins following RT, with 157 upregulated and 257 downregulated. Gene ontology analysis indicated that the majority of the dysregulated proteins were part of various metabolic pathways. Cross referencing with Mitocarta revealed a significant presence of mitochondrial proteins among the dysregulated proteins, indicating potential mitochondrial metabolic dysfunction. Further investigation with IPA analysis uncovered 76 enriched canonical pathways, 34 transcription regulators, 6 nuclear receptors, and 5 growth factors involved in RT-induced damage responses in cerebral microvessels. IPA canonical pathway analysis predicted mitochondrial dysfunction due to inhibition of various metabolic pathways in the irradiated group. Validation with western blotting confirmed the bioinformatics predictions from the proteomic dataset. Conclusions: Our data show significant proteomic changes in cerebral microvessels 6 months post-radiation, including oxidative phosphorylation, the TCA cycle, and glycolysis, suggesting metabolic mechanisms of RT-induced microvascular dysfunction.
Source: ACS Omega
Language: English
Subfield: Radiology, Nuclear Medicine and Imaging
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $1,935
OpenAlex ID: W4415557177