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  • Bandaru, SashidarGothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för laboratoriemedicin,Department of Laboratory Medicine (author)

Lack of RAC1 in macrophages protects against atherosclerosis.

  • Article/chapterEnglish2020

Publisher, publication year, extent ...

  • 2020-09-17
  • Public Library of Science (PLoS),2020

Numbers

  • LIBRIS-ID:oai:gup.ub.gu.se/296943
  • https://gup.ub.gu.se/publication/296943URI
  • https://doi.org/10.1371/journal.pone.0239284DOI
  • http://kipublications.ki.se/Default.aspx?queryparsed=id:144802654URI

Supplementary language notes

  • Language:English

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  • Subject category:ref swepub-contenttype
  • Subject category:art swepub-publicationtype

Notes

  • The Rho GTPase RAC1 is an important regulator of cytoskeletal dynamics, but the role of macrophage-specific RAC1 has not been explored during atherogenesis. We analyzed RAC1 expression in human carotid atherosclerotic plaques using immunofluorescence and found higher macrophage RAC1 expression in advanced plaques compared with intermediate human atherosclerotic plaques. We then produced mice with Rac1-deficient macrophages by breeding conditional floxed Rac1 mice (Rac1fl/fl) with mice expressing Cre from the macrophage-specific lysosome M promoter (LC). Atherosclerosis was studied in vivo by infecting Rac1fl/fl and Rac1fl/fl/LC mice with AdPCSK9 (adenoviral vector overexpressing proprotein convertase subtilisin/kexin type 9). Rac1fl/fl/LC macrophages secreted lower levels of IL-6 and TNF-α and exhibited reduced foam cell formation and lipid uptake. The deficiency of Rac1 in macrophages reduced the size of aortic atherosclerotic plaques in AdPCSK9-infected Rac1fl/fl/LC mice. Compare with controls, intima/media ratios, the size of necrotic cores, and numbers of CD68-positive macrophages in atherosclerotic plaques were reduced in Rac1-deficient mice. Moreover, we found that RAC1 interacts with actin-binding filamin A. Macrophages expressed increased RAC1 levels in advanced human atherosclerosis. Genetic inactivation of RAC1 impaired macrophage function and reduced atherosclerosis in mice, suggesting that drugs targeting RAC1 may be useful in the treatment of atherosclerosis.

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  • Ala, ChanduGothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för laboratoriemedicin,Department of Laboratory Medicine (author)
  • Ekstrand, MatiasGothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Institute of Medicine, Department of Molecular and Clinical Medicine(Swepub:gu)xemati (author)
  • Akula, Murali KGothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Institute of Medicine, Department of Molecular and Clinical Medicine (author)
  • Pedrelli, MatteoKarolinska Institutet (author)
  • Liu, XiGothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för laboratoriemedicin,Department of Laboratory Medicine (author)
  • Bergström, Göran,1964Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Institute of Medicine, Department of Molecular and Clinical Medicine(Swepub:gu)xbgort (author)
  • Håversen, Liliana,1963Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Institute of Medicine, Department of Molecular and Clinical Medicine(Swepub:gu)xhavli (author)
  • Borén, Jan,1963Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Institute of Medicine, Department of Molecular and Clinical Medicine(Swepub:gu)xborej (author)
  • Bergö, Martin O.,1970Karolinska Institutet,Gothenburg University,Göteborgs universitet,Sahlgrenska Cancer Center(Swepub:gu)xbmarl (author)
  • Akyürek, Levent,1966Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för laboratoriemedicin,Department of Laboratory Medicine(Swepub:gu)xakyle (author)
  • Göteborgs universitetInstitutionen för biomedicin, avdelningen för laboratoriemedicin (creator_code:org_t)

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  • In:PLoS One: Public Library of Science (PLoS)15:91932-6203

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