| First Author | Usui F | Year | 2012 |
| Journal | Biochem Biophys Res Commun | Volume | 425 |
| Issue | 2 | Pages | 162-8 |
| PubMed ID | 22819845 | Mgi Jnum | J:187166 |
| Mgi Id | MGI:5435627 | Doi | 10.1016/j.bbrc.2012.07.058 |
| Citation | Usui F, et al. (2012) Critical role of caspase-1 in vascular inflammation and development of atherosclerosis in Western diet-fed apolipoprotein E-deficient mice. Biochem Biophys Res Commun 425(2):162-8 |
| abstractText | 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)-1beta in the plaques as well as plasma levels of IL-1beta, IL-1alpha, IL-6, CCL2, and TNF-alpha, 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-1beta and IL-1alpha 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. |
