RRC ID 43965
Author Usui F, Shirasuna K, Kimura H, Tatsumi K, Kawashima A, Karasawa T, Hida S, Sagara J, Taniguchi S, Takahashi M.
Title Critical role of caspase-1 in vascular inflammation and development of atherosclerosis in Western diet-fed apolipoprotein E-deficient mice.
Journal Biochem Biophys Res Commun
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.
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.
Volume 425(2)
Pages 162-8
Published 2012-8-24
DOI 10.1016/j.bbrc.2012.07.058
PII S0006-291X(12)01354-X
PMID 22819845
MeSH 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
IF 2.985
Times Cited 99
Human and Animal Cells