Modelling the human IL6RA Asp358Ala variant in mice: effects on atherosclerosis and abdominal aortic aneurysm
- 1University of Cambridge
Abstract
The association of IL6RA Asp358Ala variant with reduced risk of atherosclerotic cardiovascular disease (ASCVD) and abdominal aortic aneurysm (AAA) prompted interest in targeting IL6 signalling in these conditions. A recent report that ziltivekimab, a neutralising anti-IL6 antibody, did not reduce major adverse cardiovascular events in patients with ASCVD and chronic kidney disease, has cast doubt on the causal role of IL6 signalling in ASCVD. Here, we show that introducing the orthologous IL6RA Glu357Ala substitution in male mice leads to the same alteration in soluble IL6RA levels seen in humans, and significantly prevents atherosclerosis and AAA. Thus, therapies that more closely reproduce the biological effects of the IL6RA Asp358Ala variant on IL6 signalling are needed to reduce cardiovascular risk in humans.
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BibTeX
@misc{takaoka2026modelling,
title = {{Modelling the human IL6RA Asp358Ala variant in mice: effects on atherosclerosis and abdominal aortic aneurysm}},
author = {M. Takaoka and R. Sharma and F. Lareyre and M. Clement and J. Harrison and L. Masters and Y. Lu and D. Paul and Z. Mallat},
howpublished = {bioRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.16.759391},
url = {https://www.biorxiv.org/content/10.64898/2026.10.16.759391v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Modelling the human IL6RA Asp358Ala variant in mice: effects on atherosclerosis and abdominal aortic aneurysm
AU - M. Takaoka
AU - R. Sharma
AU - F. Lareyre
AU - M. Clement
AU - J. Harrison
AU - L. Masters
AU - Y. Lu
AU - D. Paul
AU - Z. Mallat
PY - 2026
DA - 2026/10/16
PB - bioRxiv
DO - 10.64898/2026.10.16.759391
UR - https://www.biorxiv.org/content/10.64898/2026.10.16.759391v1
AB - The association of IL6RA Asp358Ala variant with reduced risk of atherosclerotic cardiovascular disease (ASCVD) and abdominal aortic aneurysm (AAA) prompted interest in targeting IL6 signalling in these conditions. A recent report that ziltivekimab, a neutralising anti-IL6 antibody, did not reduce major adverse cardiovascular events in patients with ASCVD and chronic kidney disease, has cast doubt on the causal role of IL6 signalling in ASCVD. Here, we show that introducing the orthologous IL6RA Glu357Ala substitution in male mice leads to the same alteration in soluble IL6RA levels seen in humans, and significantly prevents atherosclerosis and AAA. Thus, therapies that more closely reproduce the biological effects of the IL6RA Asp358Ala variant on IL6 signalling are needed to reduce cardiovascular risk in humans.
ER -