WFRF:(Levin Lisa)
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Arachidonate 15-Lipoxygenase Type B Knockdown Leads to Reduced Lipid Accumulation and Inflammation in Atherosclerosis
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- Magnusson, Lisa U., 1975 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Wallenberglaboratoriet,Institute of Medicine, Department of Molecular and Clinical Medicine,Wallenberg Laboratory
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- Lundqvist, Annika, 1969 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Wallenberglaboratoriet,Institute of Medicine, Department of Molecular and Clinical Medicine,Wallenberg Laboratory
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- Nurkkala Karlsson, Merja, 1966 (author)
- Gothenburg University,Göteborgs universitet,Wallenberglaboratoriet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Wallenberg Laboratory,Institute of Medicine, Department of Molecular and Clinical Medicine
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- (creator_code:org_t)
- 2012-08-17
- 2012
- English.
- In: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 7:8
- Journal article (peer-reviewed)
Abstract
Subject headings
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- 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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
Keyword
- double-edged-sword
- oxidative modification
- deficient mice
- expression
- ldl
- 8s-lipoxygenase
- identification
- interleukin-2
- angiogenesis
- macrophages
Publication and Content Type
- ref (subject category)
- art (subject category)
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- University of Gothenburg
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