title: Impairing eukaryotic elongation factor 2 kinase activity decreases atherosclerotic plaque formation.
abstract: We tested whether loss of eukaryotic elongation factor 2 kinase (eEF2K) activity in macrophages suppresses development of atherosclerosis by transplanting bone marrow from mice with mutant eEF2K into ldlr(-/-) mice. Sixteen weeks after high-fat diet feeding, mutant eEF2K hematopoietic chimeras had a dramatically reduced level of atherosclerotic plaque formation. M1-skewed macrophages from eEF2K knock-in mice have less tumour necrosis factor-α release and a lesser ability to induce expression of endothelial cell markers, providing a potential explanation for the role of eEF2K. Because eEF2K activity in cells of the hematopoietic compartment contributes to atherosclerosis development, drugs inhibiting eEF2K might have a beneficial effect in treatment of atherosclerosis.
authors.affiliation: Department of Medicine, University of British Columbia and Vancouver Coastal Health Research Institute, Vancouver, British Columbia, Canada.
authors.forename: Peng
authors.initials: P
authors.lastname: Zhang
authors.affiliation: Department of Medicine, University of British Columbia and Vancouver Coastal Health Research Institute, Vancouver, British Columbia, Canada.
authors.forename: Maziar
authors.initials: M
authors.lastname: Riazy
authors.affiliation: Biomedical Research Centre, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Matthew
authors.initials: M
authors.lastname: Gold
authors.affiliation: Department of Medicine, University of British Columbia and Vancouver Coastal Health Research Institute, Vancouver, British Columbia, Canada.
authors.forename: Shu-Huei
authors.initials: SH
authors.lastname: Tsai
authors.affiliation: Biomedical Research Centre, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Kelly
authors.initials: K
authors.lastname: McNagny
authors.affiliation: Centre for Biological Sciences, University of Southampton, Southampton, United Kingdom.
authors.forename: Christopher
authors.initials: C
authors.lastname: Proud
authors.affiliation: Department of Medicine, University of British Columbia and Vancouver Coastal Health Research Institute, Vancouver, British Columbia, Canada. Electronic address: vduronio@mail.ubc.ca.
authors.forename: Vincent
authors.initials: V
authors.lastname: Duronio
mesh_terms: D000818:Animals; D004247:DNA / Q000235:genetics*; D004195:Disease Models, Animal; D054736:Elongation Factor 2 Kinase / Q000096:biosynthesis / Q000235:genetics*; D005786:Gene Expression Regulation; D051379:Mice; D008810:Mice, Inbred C57BL; D058226:Plaque, Atherosclerotic / Q000201:enzymology* / Q000235:genetics / Q000473:pathology
chemical_list: D004247:DNA; C517690:Eef2k protein, mouse; D054736:Elongation Factor 2 Kinase