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NAMPT knockdown attenuates atherosclerosis and promotes reverse cholesterol
transport in ApoE KO mice with high-fat-induced insulin resistance
#MMPMID27229177
Li S
; Wang C
; Li K
; Li L
; Tian M
; Xie J
; Yang M
; Jia Y
; He J
; Gao L
; Boden G
; Liu H
; Yang G
Sci Rep
2016[May]; 6
(?): 26746
PMID27229177
show ga
NAMPT has been suggested association with atherosclerosis and insulin resistance.
However, the impact of NAMPT on atherosclerosis remained unknown. Therefore, the
objective of this study was to use a NAMPT loss-of-function approach to
investigate the effect of NAMPT on atherosclerosis in hypercholesterolemic mice.
We demonstrated that a specific NAMPT knockdown increased plasma HDL-C levels,
reduced the plaque area of the total aorta en face and the cross-sectional aortic
sinus, decreased macrophage number and apoptosis, and promoted RCT in HFD-fed
ApoE KO mice. These changes were accompanied by increased PPAR?, LXR?, ABCA1 and
ABCG1 expressions in the liver. NAMPT knockdown also facilitated cholesterol
efflux in RAW264.7 cells. We further investigated the effect of NAMPT knockdown
on the PPAR?-LXR? pathway of cholesterol metabolism with MK886 (a selective
inhibitor of PPAR?) in RAW264.7 macrophages. MK886 abolished the ability of NAMPT
knockdown to decrease intracellular cholesterol levels to enhance the rate of
(3)H-cholesterol efflux and to increase ABCA1/G1 and LXR? expressions in RAW264.7
macrophages. Our observations demonstrate that NAMPT knockdown exerted
antiatherogenic effects by promoting cholesterol efflux and macrophage RCT
through the PPAR?- LXR?- ABCA1/G1pathway in vitro and in vivo.
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