Caspase-1 deficiency decreases atherosclerosis in apolipoprotein E-null mice |
| |
Authors: | Gage Jessica Hasu Mirela Thabet Mohamed Whitman Stewart C |
| |
Affiliation: | Vascular Biology and Atherosclerosis Laboratory, University of Ottawa Heart Institute, Ottawa, Ontario, Canada. |
| |
Abstract: | BackgroundCaspase-1 is a cysteine protease that contributes to mammalian immunity through proteolytic activation of the proinflammatory cytokines, interleukin (IL)-1β and IL-18.MethodsTo determine if caspase-1 deficiency can protect apolipoprotein E-null (Apoe−/−) mice from atherosclerosis, gender-matched, paired-littermate Apoe−/− mice with (Casp1+/+Apoe−/−) or without (Casp1−/−Apoe−/−) a functional caspase-1 (Casp1) gene were fed either a low fat diet for 26 weeks, or a saturated fat and cholesterol-enriched diet for 8 weeks. Plasma lipids and lipoproteins were determined and atherosclerosis was quantified in the aortic sinus and aortic arch.ResultsOn either diet, caspase-1 deficiency did not affect total serum cholesterol concentrations and lipoprotein-cholesterol distributions. However, caspase-1 deficiency significantly decreased atherosclerosis in the ascending aorta by 35%-45% in both sexes of mice fed either diet. We further examined atherosclerotic lesions for 2 indices of immune cell activation: Major Histocompatibility Complex (MHC) class II and interferon (IFN)-γ expression. There was a 40%-50% reduction in the number of lesion-associated cells expressing MHC class II from both sexes of Casp1−/−Apoe−/− mice compared with Casp1+/+Apoe−/− mice and, a significant reduction in lesion-associated IFN-γ in female Casp1−/−Apoe−/− compared with their Casp1+/+Apoe−/− counterparts.ConclusionsWe conclude that caspase-1 promotes atherosclerosis by enhancing the inflammatory status of the lesion through a mechanism likely involving activation of lesion-associated immune cells and IFN-γ expression. |
| |
Keywords: | |
本文献已被 ScienceDirect PubMed 等数据库收录! |
|