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Interleukin-1 regulates multiple atherogenic mechanisms in response to fat feeding

Chamberlain, J., Francis, S., Brookes, Z., Shaw, G., Graham, D., Alp, N.J., Dower, S. and Crossman, D.C. (2009) Interleukin-1 regulates multiple atherogenic mechanisms in response to fat feeding. Plos One, 4 (4). Art No.e5073. ISSN 1932-6203

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Abstract

Background: Atherosclerosis is an inflammatory process that develops in individuals with known risk factors that include hypertension and hyperlipidaemia, influenced by diet. However, the interplay between diet, inflammatory mechanisms and vascular risk factors requires further research. We hypothesised that interleukin-1 (IL-1) signaling in the vessel wall would raise arterial blood pressure and promote atheroma.

Methodology/Principal Findings: Apoe(-/-) and Apoe(-/-)/IL-1R1(-/-) mice were fed high fat diets for 8 weeks, and their blood pressure and atherosclerosis development measured. Apoe(-/-)/IL-R1(-/-) mice had a reduced blood pressure and significantly less atheroma than Apoe(-/-) mice. Selective loss of IL-1 signaling in the vessel wall by bone marrow transplantation also reduced plaque burden (p<0.05). This was associated with an IL-1 mediated loss of endothelium-dependent relaxation and an increase in vessel wall Nox 4. Inhibition of IL-1 restored endothelium-dependent vasodilatation and reduced levels of arterial oxidative stress.

Conclusions/Significance: The IL-1 cytokine system links atherogenic environmental stimuli with arterial inflammation, oxidative stress, increased blood pressure and atherosclerosis. This is the first demonstration that inhibition of a single cytokine can block the rise in blood pressure in response to an environmental stimulus. IL-1 inhibition may have profound beneficial effects on atherogenesis in man.

Item Type: Article
Copyright, Publisher and Additional Information: © 2009 Chamberlain et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Academic Units: The University of Sheffield > Faculty of Medicine, Dentistry and Health (Sheffield) > School of Medicine (Sheffield) > Department of Cardiovascular Science
The University of Sheffield > Faculty of Science (Sheffield) > School of Biological Sciences (Sheffield) > Department of Biomedical Science (Sheffield)
Depositing User: Miss Anthea Tucker
Date Deposited: 20 Jan 2010 11:15
Last Modified: 08 Feb 2013 16:59
Published Version: http://dx.doi.org/10.1371/journal.pone.0005073
Status: Published
Publisher: Public Library Science
Refereed: Yes
Identification Number: 10.1371/journal.pone.0005073
URI: http://eprints.whiterose.ac.uk/id/eprint/10309

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