Imperial College London
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DrJamesPeters

Faculty of Medicine, Department of Immunology and Inflammation

Clinical Reader in Rheumatology
 
 
 
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j.peters

 
 
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ICTEM buildingHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Paige:2019:10.1161/CIRCGEN.118.002413,
author = {Paige, E and Clement, M and Lareyre, F and Sweeting, M and Raffort, J and Grenier, C and Finigan, A and Harrison, J and Peters, JE and Sun, BB and Butterworth, AS and Harrison, SC and Bown, MJ and Lindholt, JS and Badger, SA and Kullo, IJ and Powell, J and Norman, PE and Scott, DJA and Bailey, MA and Rose-John, S and Danesh, J and Freitag, DF and Paul, DS and Mallat, Z},
doi = {10.1161/CIRCGEN.118.002413},
journal = {Circulation: Genomic and Precision Medicine},
title = {Interleukin-6 receptor signalling and abdominal aortic aneurysm growth rates},
url = {http://dx.doi.org/10.1161/CIRCGEN.118.002413},
volume = {12},
year = {2019}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Background:The Asp358Ala variant (rs2228145; A>C) in the IL (interleukin)-6 receptor (IL6R) gene has been implicated in the development of abdominal aortic aneurysms (AAAs), but its effect on AAA growth over time is not known. We aimed to investigate the clinical association between the IL6R-Asp358Ala variant and AAA growth and to assess the effect of blocking the IL-6 signaling pathway in mouse models of aortic aneurysm rupture or dissection.Methods:Using data from 2863 participants with AAA from 9 prospective cohorts, age- and sex-adjusted mixed-effects linear regression models were used to estimate the association between the IL6R-Asp358Ala variant and annual change in AAA diameter (mm/y). In a series of complementary randomized trials in mice, the effect of blocking the IL-6 signaling pathways was assessed on plasma biomarkers, systolic blood pressure, aneurysm diameter, and time to aortic rupture and death.Results:After adjusting for age and sex, baseline aneurysm size was 0.55 mm (95% CI, 0.13–0.98 mm) smaller per copy of the minor allele [C] of the Asp358Ala variant. Change in AAA growth was −0.06 mm per year (−0.18 to 0.06) per copy of the minor allele; a result that was not statistically significant. Although all available worldwide data were used, the genetic analyses were not powered for an effect size as small as that observed. In 2 mouse models of AAA, selective blockage of the IL-6 trans-signaling pathway, but not combined blockage of both, the classical and trans-signaling pathways, was associated with improved survival (P<0.05).Conclusions:Our proof-of-principle data are compatible with the concept that IL-6 trans-signaling is relevant to AAA growth, encouraging larger-scale evaluation of this hypothesis.
AU  - Paige,E
AU  - Clement,M
AU  - Lareyre,F
AU  - Sweeting,M
AU  - Raffort,J
AU  - Grenier,C
AU  - Finigan,A
AU  - Harrison,J
AU  - Peters,JE
AU  - Sun,BB
AU  - Butterworth,AS
AU  - Harrison,SC
AU  - Bown,MJ
AU  - Lindholt,JS
AU  - Badger,SA
AU  - Kullo,IJ
AU  - Powell,J
AU  - Norman,PE
AU  - Scott,DJA
AU  - Bailey,MA
AU  - Rose-John,S
AU  - Danesh,J
AU  - Freitag,DF
AU  - Paul,DS
AU  - Mallat,Z
DO  - 10.1161/CIRCGEN.118.002413
PY  - 2019///
SN  - 2574-8300
TI  - Interleukin-6 receptor signalling and abdominal aortic aneurysm growth rates
T2  - Circulation: Genomic and Precision Medicine
UR  - http://dx.doi.org/10.1161/CIRCGEN.118.002413
UR  - http://hdl.handle.net/10044/1/67146
VL  - 12
ER  -
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