title: Critical role of caspase-1 in vascular inflammation and development of atherosclerosis in Western diet-fed apolipoprotein E-deficient mice.
abstract: OBJECTIVE
  Recent investigations have suggested that the inflammasome plays a role in the development of vascular inflammation and atherosclerosis; however, its precise role remains controversial. We produced double-deficient mice for apolipoprotien E (Apoe) and caspase-1 (Casp1), a key component molecule of the inflammasome, and investigated the effect of caspase-1 deficiency on vascular inflammation and atherosclerosis.
  
  
  RESULTS
  Atherosclerotic plaque areas in whole aortas and aortic root of Western diet (WD)-fed Apoe(-/-)Casp1(-/-) mice were significantly reduced compared to those in Apoe(-/-) mice. The amount of macrophages and vascular smooth muscle cells in the plaques was also reduced in Apoe(-/-)Casp1(-/-) mice. No significant differences in plasma lipid profiles and body weight change were observed between these mice. Expression of interleukin (IL)-1β in the plaques as well as plasma levels of IL-1β, IL-1α, IL-6, CCL2, and TNF-α, in Apoe(-/-)Casp1(-/-) mice were lower than those in Apoe(-/-) mice. In vitro experiments showed that calcium phosphate crystals induced caspase-1 activation and secretion of IL-1β and IL-1α in macrophages.
  
  
  CONCLUSIONS
  Our findings suggest that caspase-1 plays a critical role in vascular inflammation and atherosclerosis, and that modulation of caspase-1 could be a potential target for prevention and treatment of atherosclerosis.
authors: Division of Bioimaging Sciences, Center for Molecular Medicine, Jichi Medical University, Tochigi, Japan.
authors: Fumitake
authors: F
authors: Usui
authors: Koumei
authors: K
authors: Shirasuna
authors: Hiroaki
authors: H
authors: Kimura
authors: Kazuki
authors: K
authors: Tatsumi
authors: Akira
authors: A
authors: Kawashima
authors: Tadayoshi
authors: T
authors: Karasawa
authors: Shigeaki
authors: S
authors: Hida
authors: Junji
authors: J
authors: Sagara
authors: Shun'ichiro
authors: S
authors: Taniguchi
authors: Masafumi
authors: M
authors: Takahashi
mesh_terms: D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency / Q000235:genetics; D050197:Atherosclerosis / Q000201:enzymology* / Q000209:etiology / Q000235:genetics; D020170:Caspase 1 / Q000235:genetics / Q000502:physiology*; D004032:Diet / Q000009:adverse effects*; D058847:Inflammasomes / Q000378:metabolism; D008264:Macrophages / Q000201:enzymology / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D014657:Vasculitis / Q000201:enzymology* / Q000209:etiology / Q000235:genetics
chemical_list: D001057:Apolipoproteins E; D058847:Inflammasomes; D020170:Caspase 1