title: Despite antiatherogenic metabolic characteristics, SCD1-deficient mice have increased inflammation and atherosclerosis.
abstract: OBJECTIVE
  Absence of stearoyl-CoA desaturase-1 (SCD1) in mice reduces plasma triglycerides and provides protection from obesity and insulin resistance, which would be predicted to be associated with reduced susceptibility to atherosclerosis. The aim of this study was to determine the effect of SCD1 deficiency on atherosclerosis.
  
  
  RESULTS
  Despite an antiatherogenic metabolic profile, SCD1 deficiency increases atherosclerosis in hyperlipidemic low-density lipoprotein receptor (LDLR)-deficient mice challenged with a Western diet. Lesion area at the aortic root is significantly increased in males and females in two models of SCD1 deficiency. Inflammatory changes are evident in the skin of these mice, including increased intercellular adhesion molecule (ICAM)-1 and ulcerative dermatitis. Increases in ICAM-1 and interleukin-6 are also evident in plasma of SCD1-deficient mice. HDL particles demonstrate changes associated with inflammation, including decreased plasma apoA-II and apoA-I and paraoxonase-1 and increased plasma serum amyloid A. Lipopolysaccharide-induced inflammatory response and cholesterol efflux are not altered in SCD1-deficient macrophages. In addition, when SCD1 deficiency is limited to bone marrow-derived cells, lesion size is not altered in LDLR-deficient mice.
  
  
  CONCLUSIONS
  These studies reinforce the crucial role of chronic inflammation in promoting atherosclerosis, even in the presence of antiatherogenic biochemical and metabolic characteristics.
authors.affiliation: Centre for Molecular Medicine and Therapeutics, Department of Medical Genetics, University of British Columbia, and Child & Family Research Institute, 980 West 28th Avenue, Vancouver, BC, Canada V5Z 4H4.
authors.forename: Marcia L E
authors.initials: ML
authors.lastname: MacDonald
authors.forename: Miranda
authors.initials: M
authors.lastname: van Eck
authors.forename: Reeni B
authors.initials: RB
authors.lastname: Hildebrand
authors.forename: Brian W C
authors.initials: BW
authors.lastname: Wong
authors.forename: Nagat
authors.initials: N
authors.lastname: Bissada
authors.forename: Piers
authors.initials: P
authors.lastname: Ruddle
authors.forename: Anatol
authors.initials: A
authors.lastname: Kontush
authors.forename: Hala
authors.initials: H
authors.lastname: Hussein
authors.forename: Mahmoud A
authors.initials: MA
authors.lastname: Pouladi
authors.forename: M John
authors.initials: MJ
authors.lastname: Chapman
authors.forename: Catherine
authors.initials: C
authors.lastname: Fievet
authors.forename: Theo J C
authors.initials: TJ
authors.lastname: van Berkel
authors.forename: Bart
authors.initials: B
authors.lastname: Staels
authors.forename: Bruce M
authors.initials: BM
authors.lastname: McManus
authors.forename: Michael R
authors.initials: MR
authors.lastname: Hayden
mesh_terms: D000818:Animals; D001053:Apolipoproteins / Q000097:blood; D043303:Aryldialkylphosphatase / Q000097:blood; D050197:Atherosclerosis / Q000201:enzymology* / Q000235:genetics / Q000276:immunology / Q000473:pathology; D004195:Disease Models, Animal; D018450:Disease Progression; D005260:Female; D006949:Hyperlipidemias / Q000201:enzymology* / Q000235:genetics / Q000276:immunology / Q000473:pathology; D007249:Inflammation / Q000201:enzymology* / Q000235:genetics / Q000276:immunology / Q000473:pathology; D018836:Inflammation Mediators / Q000097:blood; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D008075:Lipoproteins, HDL / Q000097:blood; D008264:Macrophages / Q000201:enzymology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011973:Receptors, LDL / Q000172:deficiency / Q000235:genetics; D000685:Serum Amyloid A Protein / Q000378:metabolism; D012883:Skin Ulcer / Q000201:enzymology / Q000473:pathology; D013230:Stearoyl-CoA Desaturase / Q000172:deficiency* / Q000235:genetics; D013997:Time Factors
chemical_list: D001053:Apolipoproteins; D018836:Inflammation Mediators; D015850:Interleukin-6; D008075:Lipoproteins, HDL; D011973:Receptors, LDL; D000685:Serum Amyloid A Protein; D018799:Intercellular Adhesion Molecule-1; C490333:Scd1 protein, mouse; D013230:Stearoyl-CoA Desaturase; D043303:Aryldialkylphosphatase