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Interleukin-1 Regulates Multiple Atherogenic Mechanisms in Response to Fat Feeding

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 hypothes...

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Autores principales: Chamberlain, Janet, Francis, Sheila, Brookes, Zoe, Shaw, Gary, Graham, Delyth, Alp, Nicholas J., Dower, Steven, Crossman, David C.
Formato: Texto
Lenguaje:English
Publicado: Public Library of Science 2009
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2661361/
https://www.ncbi.nlm.nih.gov/pubmed/19347044
http://dx.doi.org/10.1371/journal.pone.0005073
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author Chamberlain, Janet
Francis, Sheila
Brookes, Zoe
Shaw, Gary
Graham, Delyth
Alp, Nicholas J.
Dower, Steven
Crossman, David C.
author_facet Chamberlain, Janet
Francis, Sheila
Brookes, Zoe
Shaw, Gary
Graham, Delyth
Alp, Nicholas J.
Dower, Steven
Crossman, David C.
author_sort Chamberlain, Janet
collection PubMed
description 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.
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spelling pubmed-26613612009-04-06 Interleukin-1 Regulates Multiple Atherogenic Mechanisms in Response to Fat Feeding Chamberlain, Janet Francis, Sheila Brookes, Zoe Shaw, Gary Graham, Delyth Alp, Nicholas J. Dower, Steven Crossman, David C. PLoS One Research Article 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. Public Library of Science 2009-04-06 /pmc/articles/PMC2661361/ /pubmed/19347044 http://dx.doi.org/10.1371/journal.pone.0005073 Text en Chamberlain et al. http://creativecommons.org/licenses/by/4.0/ 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 properly credited.
spellingShingle Research Article
Chamberlain, Janet
Francis, Sheila
Brookes, Zoe
Shaw, Gary
Graham, Delyth
Alp, Nicholas J.
Dower, Steven
Crossman, David C.
Interleukin-1 Regulates Multiple Atherogenic Mechanisms in Response to Fat Feeding
title Interleukin-1 Regulates Multiple Atherogenic Mechanisms in Response to Fat Feeding
title_full Interleukin-1 Regulates Multiple Atherogenic Mechanisms in Response to Fat Feeding
title_fullStr Interleukin-1 Regulates Multiple Atherogenic Mechanisms in Response to Fat Feeding
title_full_unstemmed Interleukin-1 Regulates Multiple Atherogenic Mechanisms in Response to Fat Feeding
title_short Interleukin-1 Regulates Multiple Atherogenic Mechanisms in Response to Fat Feeding
title_sort interleukin-1 regulates multiple atherogenic mechanisms in response to fat feeding
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2661361/
https://www.ncbi.nlm.nih.gov/pubmed/19347044
http://dx.doi.org/10.1371/journal.pone.0005073
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