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Vimentin deficiency in macrophages induces increased oxidative stress and vascular inflammation but attenuates atherosclerosis in mice
Univ Gothenburg, Dept Mol & Clin Med, Wallenberg Lab, Gothenburg, Sweden.;Sahlgrens Univ Hosp, Gothenburg, Sweden..
AstraZeneca, Strateg Planning & Operat, Cardiovasc & Metab Dis, IMED Biotech Unit, Gothenburg, Sweden..
KTH, Centres, Science for Life Laboratory, SciLifeLab. KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH). Kings Coll London, Ctr Host Microbiome Interact, Dent Inst, London SE1 9RT, England..ORCID iD: 0000-0002-4254-6090
Univ Gothenburg, Dept Mol & Clin Med, Wallenberg Lab, Gothenburg, Sweden.;Sahlgrens Univ Hosp, Gothenburg, Sweden..
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2018 (English)In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 8, article id 16973Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
NATURE PUBLISHING GROUP , 2018. Vol. 8, article id 16973
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Chemical Sciences
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URN: urn:nbn:se:kth:diva-239999DOI: 10.1038/s41598-018-34659-2ISI: 000450411700004PubMedID: 30451917Scopus ID: 2-s2.0-85056735161OAI: oai:DiVA.org:kth-239999DiVA, id: diva2:1269625
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QC 20181211

Available from: 2018-12-11 Created: 2018-12-11 Last updated: 2018-12-11Bibliographically approved

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Mardinoglu, Adil

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