Abstract
BackgroundClinical studies have shown that radiotherapy increases the risk of cardiovascular disease at irradiated sites years after exposure. However, there is a lack of biological explanations in humans. We therefore examined human blood vessels exposed to radiotherapy and studied C-reactive protein (CRP) and pentraxin 3 (PTX3), a new marker for adverse cardiovascular outcome dependent on TNF- alpha (TNFα) or interleukin-1beta (IL-1β) expression.MethodsPairs of irradiated and non-irradiated human conduit arteries and veins were harvested from the same patient during autologous free tissue transfer for cancer-reconstruction at a median time of 48 weeks after radiotherapy. Differential gene expression was studied using qRT-PCR, confirmed by immunohistochemistry and cellular origins determined by immunofluorescence.ResultsGene expression in irradiated arteries compared to non-irradiated showed a consistent up-regulation of PTX3 in all patients and in a majority of veins (p < 0.001). Both TNFα and IL-1β were increased in irradiated compared to non-irradiated arteries (p < 0.01) and IL-1β correlated to the PTX3 expression (p = 0.017). Immunohistochemical and immunofluorescence staining confirmed an increased expression of PTX3 in endothelial cells, macrophages and smooth muscle cells.ConclusionsThe sustained expression of PTX3 in arteries and veins tie biological evidence in humans to clinical studies and encourage further exploration of innate immunity in the pathogenesis of a radiation-induced vasculopathy.
Highlights
Clinical studies have shown that radiotherapy increases the risk of cardiovascular disease at irradiated sites years after exposure
Recent clinical studies show that radiotherapy against cancer increases the risk of cardiovascular diseases at the irradiated site, i.e. increased risk for stroke and acute myocardial infarction in patients treated with radiotherapy to the head/neck area and left thorax area, respectively [1,2,3,4]
pentraxin 3 (PTX3) staining was seen in Smooth muscle cell (SMC) and macrophages, in irradiated arteries
Summary
Clinical studies have shown that radiotherapy increases the risk of cardiovascular disease at irradiated sites years after exposure. Recent clinical studies show that radiotherapy against cancer increases the risk of cardiovascular diseases at the irradiated site, i.e. increased risk for stroke and acute myocardial infarction in patients treated with radiotherapy to the head/neck area and left thorax area, respectively [1,2,3,4]. This is further supported by animal experiments where radiotherapy accelerates the development of atherosclerotic lesions and induces an inflammatory plaque. Different cell types in the inflamed vascular wall, such as endothelial cells (ECs), smooth muscle cells (SMCs) and macrophages express PTX3 [14], but the function and the quantities of PTX3 expressed in different cell types is still unclear
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