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Sustained inflammation due to nuclear factor-kappa B activation in irradiated human arteries.

Abstract：

OBJECTIVES:The aim of this study was to investigate gene expression networks related to cardiovascular disease in radiated human arteries. BACKGROUND:Recent epidemiological studies have shown that radiotherapy is associated with cardiovascular disease years after treatment. However, the molecular mechanisms underlying late effects of radiation are poorly described. METHODS:Arterial biopsies from radiated and nonradiated human conduit arteries, from the same patient, were simultaneously harvested during microvascular free tissue transfer for cancer-reconstruction in 13 patients, 4 to 500 weeks from radiation treatment. Radiated and nonradiated arteries were compared, with Affymetrix (Santa Clara, California) microarrays on a subset of the material to generate candidate genes. A Taqman (Applied Biosystems, Foster City, California) low-density array of 45 selected genes was designed for analysis of the whole material. RESULTS:Thirteen genes were synchronously expressed in all patients (p = 0.0015), including CCL8, CCL3, CXCL2, DUSP5, FGFR2, HMOX1, HOXA9, IL-6, MMP-1, PTX3, RDH10, SOD2, and TNFAIP3. A majority of differentially regulated genes related to the nuclear factor-kappa B (NF-kappaB) signaling pathway and were dysregulated even years after radiation. The NF-kappaB activation was confirmed by immunohistochemistry and immunofluorescence. CONCLUSIONS:In the present study, we found sustained inflammation due to NF-kappaB activation in human radiated arteries. The results are supported by previous in vitro findings suggesting that deoxyribonucleic acid injury, after radiation, activates NF-kappaB. We also suggest that HOXA9 might be involved in the regulation of NF-kappaB activation. The observed sustained inflammatory response can explain cardiovascular disease years after radiation.

journal_name

J Am Coll Cardiol

journal_title

Journal of the American College of Cardiology

authors

Halle M,Gabrielsen A,Paulsson-Berne G,Gahm C,Agardh HE,Farnebo F,Tornvall P

doi

10.1016/j.jacc.2009.10.047

subject

Has Abstract

pub_date

2010-03-23 00:00:00

pages

1227-1236

issue

12

eissn

0735-1097

issn

1558-3597

pii

S0735-1097(10)00142-7

journal_volume

55

pub_type

杂志文章

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