Increased long-term expression of pentraxin 3 in irradiated human arteries and veins compared to internal controls from free tissue transfers

Journal of Translational Medicine

Martin Halle⁴  Per Tornvall⁵  Alberto Mantovani⁶  Barbara Bottazzi²  Caroline Gahm³  Sarah-Jayne Reilly¹  Tinna Christersdottir Björklund¹ 

[1] Department of Medicine, Center for Molecular Medicine, Karolinska Institutet, Karolinska University Hospital, 171 76, Stockholm, Sweden;Humanitas Clinical & Research Center, via Manzoni 113, 20089, Rozzano, Milan, Italy;Department of Oto-Rhino-Laryngology, Head and Neck Surgery and Department of Clinical Sciences, Intervention and Technology (CLINTEC) Karolinska Institutet, Karolinska University Hospital, 171 76, Stockholm, Sweden;Department of Molecular Medicine and Surgery, Section of Reconstructive Plastic Surgery, Karolinska Institutet, Karolinska University Hospital, 171 76, Stockholm, Sweden;Department of Clinical Science and Education, Södersjukhuset, Sjukhusbacken 10, 118 83, Stockholm, Sweden;Department of Translational Medicine, Università degli Studi di Milano, via Manzoni 113, 20089, Rozzano, Milan, Italy

关键词: Stroke and neck;    Atherosclerosis;    Cardiovascular disease;    Gene expression;    Blood vessels;    Human;    Radiotherapy;    CRP;    PTX3;   

Others  :  826400
DOI  :  10.1186/1479-5876-11-223

 received in 2013-03-13, accepted in 2013-09-18,  发布年份 2013

【 摘 要 】

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.

【 授权许可】

   
2013 Christersdottir Björklund et al.; licensee BioMed Central Ltd.

【 图 表 】

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