Critical role of caspase-1 in vascular inflammation and development of atherosclerosis in Western diet-fed apolipoprotein E-deficient mice

Biochem Biophys Res Commun. 2012 Aug 24;425(2):162-8. doi: 10.1016/j.bbrc.2012.07.058. Epub 2012 Jul 20.


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.

Methods and 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.

Conclusion: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apolipoproteins E / deficiency
  • Apolipoproteins E / genetics
  • Atherosclerosis / enzymology*
  • Atherosclerosis / etiology
  • Atherosclerosis / genetics
  • Caspase 1 / genetics
  • Caspase 1 / physiology*
  • Diet / adverse effects*
  • Inflammasomes / metabolism
  • Macrophages / enzymology
  • Macrophages / immunology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Mutant Strains
  • Vasculitis / enzymology*
  • Vasculitis / etiology
  • Vasculitis / genetics


  • Apolipoproteins E
  • Inflammasomes
  • Caspase 1