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Arachidonate 15-Lipoxygenase Type B Knockdown Leads to Reduced Lipid Accumulation and Inflammation in Atherosclerosis

Inflammation in the vascular wall is important for development of atherosclerosis. We have shown previously that arachidonate 15-lipoxygenase type B (ALOX15B) is more highly expressed in human atherosclerotic lesions than in healthy arteries. This enzyme oxidizes fatty acids to substances that promo...

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Autores principales: Magnusson, Lisa U., Lundqvist, Annika, Karlsson, Merja Nurkkala, Skålén, Kristina, Levin, Max, Wiklund, Olov, Borén, Jan, Hultén, Lillemor Mattsson
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3422220/
https://www.ncbi.nlm.nih.gov/pubmed/22912809
http://dx.doi.org/10.1371/journal.pone.0043142
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author Magnusson, Lisa U.
Lundqvist, Annika
Karlsson, Merja Nurkkala
Skålén, Kristina
Levin, Max
Wiklund, Olov
Borén, Jan
Hultén, Lillemor Mattsson
author_facet Magnusson, Lisa U.
Lundqvist, Annika
Karlsson, Merja Nurkkala
Skålén, Kristina
Levin, Max
Wiklund, Olov
Borén, Jan
Hultén, Lillemor Mattsson
author_sort Magnusson, Lisa U.
collection PubMed
description Inflammation in the vascular wall is important for development of atherosclerosis. We have shown previously that arachidonate 15-lipoxygenase type B (ALOX15B) is more highly expressed in human atherosclerotic lesions than in healthy arteries. This enzyme oxidizes fatty acids to substances that promote local inflammation and is expressed in lipid-loaded macrophages (foam cells) present in the atherosclerotic lesions. Here, we investigated the role of ALOX15B in foam cell formation in human primary macrophages and found that silencing of human ALOX15B decreased cellular lipid accumulation as well as proinflammatory cytokine secretion from macrophages. To investigate the role of ALOX15B in promoting the development of atherosclerosis in vivo, we used lentiviral shRNA silencing and bone marrow transplantation to knockdown mouse Alox15b gene expression in LDL-receptor-deficient (Ldlr (−/−)) mice. Knockdown of mouse Alox15b in vivo decreased plaque lipid content and markers of inflammation. In summary, we have shown that ALOX15B influences progression of atherosclerosis, indicating that this enzyme has an active proatherogenic role.
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spelling pubmed-34222202012-08-21 Arachidonate 15-Lipoxygenase Type B Knockdown Leads to Reduced Lipid Accumulation and Inflammation in Atherosclerosis Magnusson, Lisa U. Lundqvist, Annika Karlsson, Merja Nurkkala Skålén, Kristina Levin, Max Wiklund, Olov Borén, Jan Hultén, Lillemor Mattsson PLoS One Research Article Inflammation in the vascular wall is important for development of atherosclerosis. We have shown previously that arachidonate 15-lipoxygenase type B (ALOX15B) is more highly expressed in human atherosclerotic lesions than in healthy arteries. This enzyme oxidizes fatty acids to substances that promote local inflammation and is expressed in lipid-loaded macrophages (foam cells) present in the atherosclerotic lesions. Here, we investigated the role of ALOX15B in foam cell formation in human primary macrophages and found that silencing of human ALOX15B decreased cellular lipid accumulation as well as proinflammatory cytokine secretion from macrophages. To investigate the role of ALOX15B in promoting the development of atherosclerosis in vivo, we used lentiviral shRNA silencing and bone marrow transplantation to knockdown mouse Alox15b gene expression in LDL-receptor-deficient (Ldlr (−/−)) mice. Knockdown of mouse Alox15b in vivo decreased plaque lipid content and markers of inflammation. In summary, we have shown that ALOX15B influences progression of atherosclerosis, indicating that this enzyme has an active proatherogenic role. Public Library of Science 2012-08-17 /pmc/articles/PMC3422220/ /pubmed/22912809 http://dx.doi.org/10.1371/journal.pone.0043142 Text en © 2012 Magnusson 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
Magnusson, Lisa U.
Lundqvist, Annika
Karlsson, Merja Nurkkala
Skålén, Kristina
Levin, Max
Wiklund, Olov
Borén, Jan
Hultén, Lillemor Mattsson
Arachidonate 15-Lipoxygenase Type B Knockdown Leads to Reduced Lipid Accumulation and Inflammation in Atherosclerosis
title Arachidonate 15-Lipoxygenase Type B Knockdown Leads to Reduced Lipid Accumulation and Inflammation in Atherosclerosis
title_full Arachidonate 15-Lipoxygenase Type B Knockdown Leads to Reduced Lipid Accumulation and Inflammation in Atherosclerosis
title_fullStr Arachidonate 15-Lipoxygenase Type B Knockdown Leads to Reduced Lipid Accumulation and Inflammation in Atherosclerosis
title_full_unstemmed Arachidonate 15-Lipoxygenase Type B Knockdown Leads to Reduced Lipid Accumulation and Inflammation in Atherosclerosis
title_short Arachidonate 15-Lipoxygenase Type B Knockdown Leads to Reduced Lipid Accumulation and Inflammation in Atherosclerosis
title_sort arachidonate 15-lipoxygenase type b knockdown leads to reduced lipid accumulation and inflammation in atherosclerosis
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3422220/
https://www.ncbi.nlm.nih.gov/pubmed/22912809
http://dx.doi.org/10.1371/journal.pone.0043142
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