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

Tinna Christersdottir Björklund, Sarah Jayne Reilly, Caroline Gahm, Barbara Bottazzi, Alberto Mantovani, Per Tornvall, Martin Halle

Research output: Contribution to journalArticle

11 Citations (Scopus)

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.

Original languageEnglish
Article number223
JournalJournal of Translational Medicine
Volume11
Issue number1
DOIs
Publication statusPublished - Sep 18 2013

Fingerprint

Veins
Arteries
Tissue
Radiotherapy
Interleukin-1beta
Gene expression
Fluorescent Antibody Technique
Gene Expression
Macrophages
Endothelial cells
Blood vessels
Innate Immunity
C-Reactive Protein
Smooth Muscle Myocytes
Blood Vessels
Muscle
Cardiovascular Diseases
Up-Regulation
Endothelial Cells
Tumor Necrosis Factor-alpha

Keywords

  • Atherosclerosis
  • Blood vessels
  • Cardiovascular disease
  • CRP
  • Gene expression
  • Human
  • PTX3
  • Radiotherapy
  • Stroke and neck

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Increased long-term expression of pentraxin 3 in irradiated human arteries and veins compared to internal controls from free tissue transfers. / Christersdottir Björklund, Tinna; Reilly, Sarah Jayne; Gahm, Caroline; Bottazzi, Barbara; Mantovani, Alberto; Tornvall, Per; Halle, Martin.

In: Journal of Translational Medicine, Vol. 11, No. 1, 223, 18.09.2013.

Research output: Contribution to journalArticle

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N2 - 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.

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