Increased long-term expression of pentraxin 3 in irradiated human arteries and veins compared to internal controls from
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RESEARCH
Open Access
Increased long-term expression of pentraxin 3 in irradiated human arteries and veins compared to internal controls from free tissue transfers Tinna Christersdottir Björklund1, Sarah-Jayne Reilly1, Caroline Gahm2, Barbara Bottazzi5, Alberto Mantovani5,6, Per Tornvall3 and Martin Halle4*
Abstract Background: Clinical 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. Methods: Pairs 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. Results: Gene 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. Conclusions: The 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. Keywords: PTX3, CRP, Radiotherapy, Human, Blood vessels, Gene expression, Cardiovascular disease, Atherosclerosis, Stroke and neck
Background 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 [1-4]. This is further supported by animal experiments where radiotherapy accelerates the development of atherosclerotic lesions and induces an inflammatory plaque
* Correspondence: [email protected] 4 Department of Molecular Medicine and Surgery, Section of Reconstructive Plastic Surgery, Karolinska Institutet, Karolinska University Hospital, 171 76, Stockholm, Sweden Full list of author information is available at the end of the article
phenotype in ApoE−/− mice [5]. However, there is a paucity of studies in humans and animal experiments are limited by short life cycles since adverse clinical outcomes are not evident until years after radiotherapy exposure in the clinical situation [3,6]. As the incidence of cancer increases and cancer patients survive
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