当前位置： SCI文献检索 > ATHEROSCLEROSIS期刊下所有文献 > Selective inhibition of endothelial NF-κB signaling attenuates chronic intermittent hypoxia-induced atherosclerosis in mice.

Selective inhibition of endothelial NF-κB signaling attenuates chronic intermittent hypoxia-induced atherosclerosis in mice.

Abstract：

BACKGROUND AND AIMS:Chronic intermittent hypoxia (CIH) exposure causes atherosclerosis, although the underlying mechanisms are poorly understood. This study defines the role of endothelial intrinsic NF-κB signaling in the atherogenic response to CIH. METHODS:We created ApoE-ECI-κBmt mice that are deficient in the apolipoprotein E gene (ApoE-/-) and overexpress an I-κBα mutant (I-κBmt) selectively in endothelial cells. ApoE-/- and ApoE-ECI-κBmt mice were fed a normal chow diet (NCD) or high cholesterol diet (HCD) and exposed to sham or CIH, and atherosclerotic lesions were quantified. RESULTS:CIH exposure activated NF-κB in aortas, and induced the expression of endothelial-specific and NF-κB-dependent genes, E-selectin and vascular cell adhesion molecule (VCAM)-1, in the aortas and hearts. Endothelial I-κBmt overexpression in ApoE-ECI-κBmt mice significantly inhibited CIH-induced NF-κB activity, and suppressed E-selectin and VCAM-1 expressions, confirming endothelial NF-κB inhibition in ApoE-ECI-κBmt mice. ApoE-/- mice, on NCD, developed mild atherosclerotic lesions spontaneously, and developed advanced and larger areas of atherosclerotic plaques when exposed to CIH. ApoE-/- mice also developed advanced atherosclerotic lesions when fed an HCD alone. The HCD-induced atherosclerotic plaques became more advanced, and plaque area was doubled in mice exposed to HCD + CIH. Endothelial I-κBmt overexpression in ApoE-ECI-κBmt mice attenuated spontaneously developed atherosclerotic lesions, abrogated CIH-induced atherosclerosis and mitigated CIH-mediated facilitation of HCD-induced atherosclerosis. CONCLUSIONS:These results suggest that endothelial intrinsic NF-kB signaling may play a pivotal role in CIH-induced atherosclerosis.

journal_name

Atherosclerosis

journal_title

Atherosclerosis

authors

Song D,Fang G,Mao SZ,Ye X,Liu G,Miller EJ,Greenberg H,Liu SF

doi

10.1016/j.atherosclerosis.2018.01.027

subject

Has Abstract

pub_date

2018-03-01 00:00:00

pages

68-75

eissn

0021-9150

issn

1879-1484

pii

S0021-9150(18)30028-5

journal_volume

270

pub_type

杂志文章

在线工具

Selective inhibition of endothelial NF-κB signaling attenuates chronic intermittent hypoxia-induced atherosclerosis in mice.