title: Caspase-1 deficiency decreases atherosclerosis in apolipoprotein E-null mice.
abstract: BACKGROUND
  Caspase-1 is a cysteine protease that contributes to mammalian immunity through proteolytic activation of the proinflammatory cytokines, interleukin (IL)-1β and IL-18.
  
  
  METHODS
  To determine if caspase-1 deficiency can protect apolipoprotein E-null (Apoe(-/-)) mice from atherosclerosis, gender-matched, paired-littermate Apoe(-/-) mice with (Casp1(+/+)Apoe(-/-)) or without (Casp1(-/-)Apoe(-/-)) a functional caspase-1 (Casp1) gene were fed either a low fat diet for 26 weeks, or a saturated fat and cholesterol-enriched diet for 8 weeks. Plasma lipids and lipoproteins were determined and atherosclerosis was quantified in the aortic sinus and aortic arch.
  
  
  RESULTS
  On either diet, caspase-1 deficiency did not affect total serum cholesterol concentrations and lipoprotein-cholesterol distributions. However, caspase-1 deficiency significantly decreased atherosclerosis in the ascending aorta by 35%-45% in both sexes of mice fed either diet. We further examined atherosclerotic lesions for 2 indices of immune cell activation: Major Histocompatibility Complex (MHC) class II and interferon (IFN)-γ expression. There was a 40%-50% reduction in the number of lesion-associated cells expressing MHC class II from both sexes of Casp1(-/-)Apoe(-/-) mice compared with Casp1(+/+)Apoe(-/-) mice and, a significant reduction in lesion-associated IFN-γ in female Casp1(-/-)Apoe(-/-) compared with their Casp1(+/+)Apoe(-/-) counterparts.
  
  
  CONCLUSIONS
  We conclude that caspase-1 promotes atherosclerosis by enhancing the inflammatory status of the lesion through a mechanism likely involving activation of lesion-associated immune cells and IFN-γ expression.
authors.affiliation: Vascular Biology and Atherosclerosis Laboratory, University of Ottawa Heart Institute, Ottawa, Ontario, Canada.
authors.forename: Jessica
authors.initials: J
authors.lastname: Gage
authors.forename: Mirela
authors.initials: M
authors.lastname: Hasu
authors.forename: Mohamed
authors.initials: M
authors.lastname: Thabet
authors.forename: Stewart C
authors.initials: SC
authors.lastname: Whitman
mesh_terms: D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics*; D050197:Atherosclerosis / Q000235:genetics*; D020170:Caspase 1 / Q000172:deficiency* / Q000235:genetics; D004195:Disease Models, Animal; D005260:Female; D008297:Male; D051379:Mice; D018345:Mice, Knockout
chemical_list: D001057:Apolipoproteins E; D020170:Caspase 1