Key result
Ionizing radiation exposure is linked to higher PAI-1 gene expression in arteries and veins.
Why the study?
Radiotherapy can induce vascular disease at the site of exposure, but the underlying biology and sustained molecular changes remain unclear.
Does prior radiotherapy contribute to sustained expression of PAI-1 in human arteries and veins?
Observational
Does prior radiotherapy contribute to sustained expression of PAI-1 in human arteries and veins?
Radiotherapy induces sustained upregulation of PAI-1 in the adventitia of arteries and veins, suggesting chronic inflammation that may contribute to radiation-induced vascular disease.
Answers are grounded in this paper and cite their sources.
PAI-1 upregulation in irradiated vessels may reflect chronic inflammation; hypothesis-generating for radiation vasculopathy and requires prospective validation.
Background. Clinical studies have shown that radiotherapy can induce vascular disease at the site of exposure but is usually not clinically evident until years after treatment. We have studied irradiated human arteries and veins to better understand the underlying biology in search of future treatments. The aim was to investigate whether radiotherapy contributed to a sustained expression of plasminogen activator inhibitor-1 (PAI-1) in human arteries and veins. Methods. Irradiated arteries and veins were harvested, together with unirradiated control vessels, from patients undergoing free tissue transfer reconstruction at a median time of 90 weeks [5–650] following radiation exposure. Differential gene expression of PAI-1 was analysed, together with immunohistochemistry (IHC) and immunofluorescence (IF). Results. PAI-1 gene expression was increased in both arteries ( p=0.012 ) and veins ( p<0.001 ) in irradiated compared to unirradiated control vessels. IHC and IF indicated that cells expressing PAI-1 were located in the adventitia of both arteries and veins and colocalized with cells positive for CD68, CD45, and α-SMA in arteries and with CD45 and α-SMA in veins. Conclusion. The current study shows a sustained upregulation of PAI-1 in both arteries and veins after exposure to ionizing radiation, indicating a chronic inflammation mainly in the adventitia. We believe that the results contribute to further understanding of radiation-induced vascular disease, where targeting PAI-1 may be a potential treatment.
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Eriksson et al. (2018) conducted an observational in Cancer patients undergoing free tissue transfer reconstruction. Ionizing radiation vs. Unirradiated control vessels was evaluated on PAI-1 gene expression (p=0.012 (arteries), <0.001 (veins)). Exposure to ionizing radiation significantly increased PAI-1 gene expression in both arteries (p=0.012) and veins (p<0.001) compared to unirradiated control vessels.
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