Accumulation of macrophage"foam"cells,laden with cholesterol and cholesteryl ester,within the intima of large arteries,is a hallmark of early"fatty streak"lesions which can progress to complex,mult...Accumulation of macrophage"foam"cells,laden with cholesterol and cholesteryl ester,within the intima of large arteries,is a hallmark of early"fatty streak"lesions which can progress to complex,multicellular atheromatous plaques,involving lipoproteins from the bloodstream and cells of the innate and adaptive immune response.Sterol accumulation triggers induction of genes encoding proteins mediating the atheroprotective cholesterol efflux pathway.Within the arterial intima,however,this mechanism is overwhelmed,leading to distinct changes in macrophage phenotype and inflammatory status.Over the last decade marked gains have been made in understanding of the epigenetic landscape which influence macrophage function,and in particular the importance of small non-coding micro-RNA(miRNA)sequences in this context.This review identifies some of the miRNA sequences which play a key role in regulating"foam"cell formation and atherogenesis,highlighting sequences involved in cholesterol accumulation,those influencing inflammation in sterol-loaded cells,and novel sequences and pathways which may offer new strategies to influence macrophage function within atherosclerotic lesions.展开更多
Objective： To observe the effect of andrographolide on the activation of mitogen-activated protein kinases （MAPKs） and expression of nuclear factor- kB （NF-kB） in macrophage foam cells. Methods： The mouse perito...Objective： To observe the effect of andrographolide on the activation of mitogen-activated protein kinases （MAPKs） and expression of nuclear factor- kB （NF-kB） in macrophage foam cells. Methods： The mouse peritoneal macrophages were cultured in the media in the presence of oxidized low-density lipoprotein （ox-LDL）, ox-LDL＋andrographolide, or neither （control）. The phosphorylation of MAPK molecules （p38MAPK, JNK, ERK1/2） and the expressions of NK- kB p65 were examined by Western blot. Results： As compared with cells in the control group, the expressions of phospho-p38 and NF- kB p65 were increased in the cells cultured with either ox-LDL or ox-LDL＋andrographolide （P〈0.01）, but attenuated significantly in the presence of ox-LDL＋ andrographolide when compared with ox-LDL （P〈0.05）. The phospho-JNK increased in the presence of either ox-LDL or ox-LDL＋andrographolide when compared with control cells （P〈0.01）, but no significant difference existed between ox-LDL and ox-LDL＋andrographolide （P〉0.05）. The expression of phospho-ERK1/2 was increased in the presence of ox-LDL compared with the control cells （P〈0.01）, but no significant differences existed between the cells cultured in the presence of ox-LDL＋andrographolide and the control medium （P〉0.05）. Conclusions： Andrographolide could inhibit the activation of ERK1/2, p38MAPK and NK-kB induced by ox-LDL in macrophage foam cells, which might be one of its mechanisms in preventing atherosclerosis.展开更多
文摘Accumulation of macrophage"foam"cells,laden with cholesterol and cholesteryl ester,within the intima of large arteries,is a hallmark of early"fatty streak"lesions which can progress to complex,multicellular atheromatous plaques,involving lipoproteins from the bloodstream and cells of the innate and adaptive immune response.Sterol accumulation triggers induction of genes encoding proteins mediating the atheroprotective cholesterol efflux pathway.Within the arterial intima,however,this mechanism is overwhelmed,leading to distinct changes in macrophage phenotype and inflammatory status.Over the last decade marked gains have been made in understanding of the epigenetic landscape which influence macrophage function,and in particular the importance of small non-coding micro-RNA(miRNA)sequences in this context.This review identifies some of the miRNA sequences which play a key role in regulating"foam"cell formation and atherogenesis,highlighting sequences involved in cholesterol accumulation,those influencing inflammation in sterol-loaded cells,and novel sequences and pathways which may offer new strategies to influence macrophage function within atherosclerotic lesions.
文摘Objective： To observe the effect of andrographolide on the activation of mitogen-activated protein kinases （MAPKs） and expression of nuclear factor- kB （NF-kB） in macrophage foam cells. Methods： The mouse peritoneal macrophages were cultured in the media in the presence of oxidized low-density lipoprotein （ox-LDL）, ox-LDL＋andrographolide, or neither （control）. The phosphorylation of MAPK molecules （p38MAPK, JNK, ERK1/2） and the expressions of NK- kB p65 were examined by Western blot. Results： As compared with cells in the control group, the expressions of phospho-p38 and NF- kB p65 were increased in the cells cultured with either ox-LDL or ox-LDL＋andrographolide （P〈0.01）, but attenuated significantly in the presence of ox-LDL＋ andrographolide when compared with ox-LDL （P〈0.05）. The phospho-JNK increased in the presence of either ox-LDL or ox-LDL＋andrographolide when compared with control cells （P〈0.01）, but no significant difference existed between ox-LDL and ox-LDL＋andrographolide （P〉0.05）. The expression of phospho-ERK1/2 was increased in the presence of ox-LDL compared with the control cells （P〈0.01）, but no significant differences existed between the cells cultured in the presence of ox-LDL＋andrographolide and the control medium （P〉0.05）. Conclusions： Andrographolide could inhibit the activation of ERK1/2, p38MAPK and NK-kB induced by ox-LDL in macrophage foam cells, which might be one of its mechanisms in preventing atherosclerosis.
