TY - JOUR
T1 - Endothelial cell-specific NF-kappaB inhibition protects mice from atherosclerosis
AU - Gareus, Ralph
AU - Kotsaki, Elena
AU - Xanthoulea, Sofia
AU - van der Made, Ingeborg
AU - Gijbels, Marion J. J.
AU - Kardakaris, Rozina
AU - Polykratis, Apostolos
AU - Kollias, George
AU - de Winther, Menno P. J.
AU - Pasparakis, Manolis
PY - 2008
Y1 - 2008
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
AB - 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
U2 - https://doi.org/10.1016/j.cmet.2008.08.016
DO - https://doi.org/10.1016/j.cmet.2008.08.016
M3 - Article
C2 - 19046569
SN - 1550-4131
VL - 8
SP - 372
EP - 383
JO - Cell metabolism
JF - Cell metabolism
IS - 5
ER -