Inhibition of ERK1/2 and Activation of XXXX Synergistically Reduce Atherosclerotic Lesions in @entity6970 -Deficient @entity19 .

@entity2298 @entity23711 @entity6970 @entity5732 @entity1560 @entity844 @entity2299 @entity19 @entity23710 @entity75 @entity8838 @entity731 @entity18340 @entity99 @entity165
OBJECTIVE: Activation of @entity23710 ( @entity23710 ) inhibits @entity731 but induces @entity2298 . In vitro, it has been shown that @entity8838 ( @entity8838 ) inhibitor synergizes @entity23710 ligand-induced macrophage @entity23711 expression and @entity165 efflux. In this study, we determined whether @entity8838 ( @entity5732 ) and @entity23710 ligand ( @entity18340 ) can have a synergistic effect on the reduction of @entity731 while eliminating @entity23710 ligand-induced @entity1560 and @entity2298 . We also set out to identify the cellular mechanisms of the actions. APPROACH AND RESULTS: Wild-type @entity19 were used to determine the effect of @entity5732 on a high-fat diet or high-fat diet plus @entity18340 -induced @entity2299 and @entity99 . @entity6970 deficient ( @entity6970 (-/-)) @entity19 or @entity19 with advanced lesions were used to determine the effect of the combination of @entity18340 and @entity5732 on @entity731 and @entity2298 . We found that @entity5732 protected animals against @entity18340 -induced transient or long-term hepatic lipid accumulation, @entity99 , and @entity2298 . Meanwhile, the combination of @entity18340 and @entity5732 inhibited the development of @entity731 in a synergistic manner and @entity75 . Mechanistically, in addition to synergistic induction of macrophage @entity23711 expression, the combination of @entity5732 and @entity18340 maintained arterial wall integrity, inhibited macrophage accumulation in aortas and formation of macrophages/foam cells, and activated reverse @entity165 transport. The inhibition of @entity18340 -induced lipid accumulation by the combined @entity5732 might be attributed to inactivation of lipogenesis and activation of lipolysis/ @entity844 oxidation pathways. CONCLUSIONS: Our study suggests that the combination of @entity8838 inhibitor and @entity23710 ligand can function as a novel therapy to synergistically reduce @entity731 while eliminating @entity23710 -induced deleterious effects.
