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

Autor: Shigeaki Hida, Koumei Shirasuna, Junji Sagara, Akira Kawashima, Fumitake Usui, Kazuki Tatsumi, Shun'ichiro Taniguchi, Tadayoshi Karasawa, Hiroaki Kimura, Masafumi Takahashi
Rok vydání: 2012
Předmět:
Zdroj: Biochemical and Biophysical Research Communications. 425:162-168
ISSN: 0006-291X
DOI: 10.1016/j.bbrc.2012.07.058
Popis: 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.
Databáze: OpenAIRE
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