| First Author | Gareus R | Year | 2008 |
| Journal | Cell Metab | Volume | 8 |
| Issue | 5 | Pages | 372-83 |
| PubMed ID | 19046569 | Mgi Jnum | J:143751 |
| Mgi Id | MGI:3828900 | Doi | 10.1016/j.cmet.2008.08.016 |
| Citation | Gareus R, et al. (2008) Endothelial cell-specific NF-kappaB inhibition protects mice from atherosclerosis. Cell Metab 8(5):372-83 |
| abstractText | Atherosclerosis is a progressive disorder of the arterial wall and the underlying cause of cardiovascular diseases such as heart attack and stroke. Today, atherosclerosis is recognized as a complex disease with a strong inflammatory component. The nuclear factor-kappaB (NF-kappaB) signaling pathway regulates inflammatory responses and has been implicated in atherosclerosis. Here, we addressed the function of NF-kappaB signaling in vascular endothelial cells in the pathogenesis of atherosclerosis in vivo. Endothelium-restricted inhibition of NF-kappaB activation, achieved by ablation of NEMO/IKKgamma or expression of dominant-negative IkappaBalpha specifically in endothelial cells, resulted in strongly reduced atherosclerotic plaque formation in ApoE(-/-) mice fed with a cholesterol-rich diet. Inhibition of NF-kappaB abrogated adhesion molecule induction in endothelial cells, impaired macrophage recruitment to atherosclerotic plaques, and reduced expression of cytokines and chemokines in the aorta. Thus, endothelial NF-kappaB signaling orchestrates proinflammatory gene expression at the arterial wall and promotes the pathogenesis of atherosclerosis. |
