Endothelial cell-specific NF-kappaB inhibition protects mice from atherosclerosis. Export

@article{citeulike:3790659, abstract = {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.}, author = {Gareus, R. and Kotsaki, E. and Xanthoulea, S. and van der Made, I. and Gijbels, M. J. and Kardakaris, R. and Polykratis, A. and Kollias, G. and de Winther, M. P. and Pasparakis, M.}, citeulike-article-id = {3790659}, citeulike-linkout-0 = {http://dx.doi.org/10.1016/j.cmet.2008.08.016}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/19046569}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=19046569}, doi = {10.1016/j.cmet.2008.08.016}, issn = {1932-7420}, journal = {Cell metabolism}, keywords = {cardiovascular-disease, endothelium, nf-kb}, month = {November}, number = {5}, pages = {372--383}, posted-at = {2008-12-16 01:17:34}, priority = {2}, title = {Endothelial cell-specific NF-kappaB inhibition protects mice from atherosclerosis.}, url = {http://dx.doi.org/10.1016/j.cmet.2008.08.016}, volume = {8}, year = {2008} }

TY - JOUR ID - citeulike:3790659 L3 - citeulike-article-id:3790659 N2 - 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. IS - 5 JF - Cell metabolism SN - 1932-7420 EP - 383 TI - Endothelial cell-specific NF-kappaB inhibition protects mice from atherosclerosis. VL - 8 SP - 372 KW - cardiovascular-disease KW - endothelium KW - nf-kb AU - Gareus, R AU - Kotsaki, E AU - Xanthoulea, S AU - van der Made, I AU - Gijbels, MJ AU - Kardakaris, R AU - Polykratis, A AU - Kollias, G AU - de Winther, MP AU - Pasparakis, M PY - 2008/11// UR - http://dx.doi.org/10.1016/j.cmet.2008.08.016 ER -