Abstract 13346: Overexpression of NF-κB p65 in Macrophages Ameliorates Atherosclerosis in ApoE Knockout Mice by Altering Lipid Metabolism
The transcription factor NF-κB is involved in the pathology of atherosclerosis. However, the role of NF-kB is not well defined in macrophage in the development of atherosclerosis. We investigated atherosclerosis formation in apoE-KO mice after NF-kB p65 overexpression in macrophages. We generated transgenic mice overexpressing NF-kB p65 in macrophages and then obtained the transgenic mice in apoE knockout (KO) gene background. The p65 overexpression increases NF-kB transcriptional activity in macrophages of apoE KO mice (p65-apoE mice). On an atherogenic diet, atherosclerotic lessen was reduced by 40% in p65-apoE mice compared with the apoE control mice (N=12). p65-apoE mice were leaner from reduced fat mass and their energy expenditure were elevated. In vitro, foam cell formation was suppressed in the p65 overexpression macrophages. The mechanisms are: 1) an increase in fatty acid oxidation and mitochondria uncoupling which is indicated by the increased PGC-1α and UCP-1 gene expression; 2) a reduced expression of scavenger receptor CD36 in microphages; 3) an enhanced antioxidation ability in the macrophages; 4) a strong induction of the anti-inflammatory cytokines IL-10 and IL-1 receptor antagonist (IL-1Ra) in macrophages; 5) a reduced plasma IL-1β; 6) an enhanced energy expenditure in TG mice. Our data suggests that activation of NF-κB in macrophages has atheroprotective effects in mice by enhancing lipid metabolism in macrophages.
- © 2012 by American Heart Association, Inc.