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Vimentin deficiency in macrophages induces increased oxidative stress and vascular inflammation but attenuates atherosclerosis in mice

Håversen, Liliana, 1963 (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,Univ Gothenburg, Dept Mol & Clin Med, Wallenberg Lab, Gothenburg, Sweden.;Sahlgrens Univ Hosp, Gothenburg, Sweden.
Sundelin, J. P. (author)
AstraZeneca, Strateg Planning & Operat, Cardiovasc & Metab Dis, IMED Biotech Unit, Gothenburg, Sweden.
Mardinoglu, Adil (author)
KTH,Science for Life Laboratory, SciLifeLab,Skolan för kemi, bioteknologi och hälsa (CBH),Kings Coll London, Ctr Host Microbiome Interact, Dent Inst, London SE1 9RT, England.
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Rutberg, Mikael, 1959 (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,Univ Gothenburg, Dept Mol & Clin Med, Wallenberg Lab, Gothenburg, Sweden.;Sahlgrens Univ Hosp, Gothenburg, Sweden.
Ståhlman, Marcus, 1975 (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,Univ Gothenburg, Dept Mol & Clin Med, Wallenberg Lab, Gothenburg, Sweden.;Sahlgrens Univ Hosp, Gothenburg, Sweden.
Wilhelmsson, Ulrika, 1970 (author)
Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för klinisk neurovetenskap,Institute of Neuroscience and Physiology, Department of Clinical Neuroscience,Univ Gothenburg, Dept Clin Neurosci, Ctr Brain Repair, Gothenburg, Sweden.
Mattsson Hultén, Lillemor, 1951 (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,Univ Gothenburg, Dept Mol & Clin Med, Wallenberg Lab, Gothenburg, Sweden.;Sahlgrens Univ Hosp, Gothenburg, Sweden.
Pekny, Milos, 1965 (author)
Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för klinisk neurovetenskap,Institute of Neuroscience and Physiology, Department of Clinical Neuroscience,Univ Gothenburg, Dept Clin Neurosci, Ctr Brain Repair, Gothenburg, Sweden.
Fogelstrand, Per, 1971 (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,Univ Gothenburg, Dept Mol & Clin Med, Wallenberg Lab, Gothenburg, Sweden.;Sahlgrens Univ Hosp, Gothenburg, Sweden.
Bentzon, J. F. (author)
Aarhus Univ, Dept Clin Med, Aarhus, Denmark.;Ctr Nacl Invest Cardiovasc Carlos III CNIC, Madrid, Spain.
Levin, Malin, 1973 (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,Univ Gothenburg, Dept Mol & Clin Med, Wallenberg Lab, Gothenburg, Sweden.;Sahlgrens Univ Hosp, Gothenburg, Sweden.
Borén, Jan, 1963 (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,Univ Gothenburg, Dept Mol & Clin Med, Wallenberg Lab, Gothenburg, Sweden.;Sahlgrens Univ Hosp, Gothenburg, Sweden.
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 (creator_code:org_t)
2018-11-19
2018
English.
In: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 8
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  • Journal article (peer-reviewed)
Abstract Subject headings
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  • The aim was to clarify the role of vimentin, an intermediate filament protein abundantly expressed in activated macrophages and foam cells, in macrophages during atherogenesis. Global gene expression, lipid uptake, ROS, and inflammation were analyzed in bone-marrow derived macrophages from vimentin-deficient (Vim(-/-)) and wild-type (Vim(-/-)) mice. Atherosclerosis was induced in Ldlr(-/-) mice transplanted with a PCSK9 gain-of-function virus. The mice were fed an atherogenic diet for 12-15 weeks. We observed impaired uptake of native LDL but increased uptake of oxLDL in Vim(-/-) macrophages. FACS analysis revealed increased surface expression of the scavenger receptor CD36 on Vim(-/-) macrophages. Vim(-/-) macrophages also displayed increased markers of oxidative stress, activity of the transcription factor NF-kappa B, secretion of proinflammatory cytokines and GLUT1-mediated glucose uptake. Vim(-/- )mice displayed decreased atherogenesis despite increased vascular inflammation and increased CD36 expression on macrophages in two mouse models of atherosclerosis. We demonstrate that vimentin has a strong suppressive effect on oxidative stress and that Vim(-/-) mice display increased vascular inflammation with increased CD36 expression on macrophages despite decreased subendothelial lipid accumulation. Thus, vimentin has a key role in regulating inflammation in macrophages during atherogenesis.

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)
NATURVETENSKAP  -- Kemi (hsv//swe)
NATURAL SCIENCES  -- Chemical Sciences (hsv//eng)

Keyword

low-density-lipoprotein
scavenger receptor
intermediate-filaments
lesion development
cd36
retention
activation
expression
identification
cholesterol
Science & Technology - Other Topics
lch j
1957
journal of biological chemistry
v226
p497

Publication and Content Type

ref (subject category)
art (subject category)

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