Increased long-term expression of pentraxin 3 in irradiated human arteries and veins compared to internal controls from free tissue transfers.
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.
Department of Molecular Medicine and Surgery, Section of Reconstructive Plastic Surgery, Karolinska Institutet, Karolinska University Hospital, 171 76, Stockholm, Sweden. martin.halle@karolinska.se.
Tinna
T
Christersdottir Björklund
Sarah-Jayne
SJ
Reilly
Caroline
C
Gahm
Barbara
B
Bottazzi
Alberto
A
Mantovani
Per
P
Tornvall
Martin
M
Halle
D000328:Adult; D000368:Aged; D001158:Arteries / Q000378:metabolism* / Q000528:radiation effects*; D002097:C-Reactive Protein / Q000235:genetics* / Q000378:metabolism; D003710:Demography; D042783:Endothelial Cells / Q000378:metabolism; D005260:Female; D058752:Free Tissue Flaps; D005786:Gene Expression Regulation; D006801:Humans; D007150:Immunohistochemistry; D008264:Macrophages / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D032389:Myocytes, Smooth Muscle / Q000378:metabolism; D000683:Serum Amyloid P-Component / Q000235:genetics* / Q000378:metabolism; D013997:Time Factors; D014680:Veins / Q000378:metabolism* / Q000528:radiation effects*; D000099153:Pentraxins
D002097:C-Reactive Protein; D000683:Serum Amyloid P-Component; D000099153:Pentraxins