Atherosclerosis is a chronic,inflammatory disorder characterized by the deposition of excess lipids in the arterial intima.The formation of macrophage-derived foam cells in a plaque is a hallmark of the development of...Atherosclerosis is a chronic,inflammatory disorder characterized by the deposition of excess lipids in the arterial intima.The formation of macrophage-derived foam cells in a plaque is a hallmark of the development of atherosclerosis.Lipid homeostasis,especially cho-lesterol homeostasis,plays a crucial role during the formation of foam cells.Recently,lipid droplet-associated proteins,including PAT and CIDE family proteins,have been shown to control the development of athero-sclerosis by regulating the formation,growth,stabiliza-tion and functions of lipid droplets in macrophage-derived foam cells.This review focuses on the potential mechanisms of formation of macrophage-derived foam cells in atherosclerosis with particular emphasis on the role of lipid homeostasis and lipid droplet-associated proteins.Understanding the process of foam cell for-mation will aid in the future discovery of novel thera-peutic interventions for atherosclerosis.展开更多
Berberine is identified to lower the serum cholesterol level in human and hamster through the induction of low density lipoproteins （LDL） receptor in hepatic cells. To evaluate its potential in preventing atheroscle...Berberine is identified to lower the serum cholesterol level in human and hamster through the induction of low density lipoproteins （LDL） receptor in hepatic cells. To evaluate its potential in preventing atherosclerosis, the effect of berberine on atherosclerosis development in apolipoprotcin E-deficient （apoE^-/-） mice was investigated. In apoE^-/- mice, berberine induced in rivo foam cell formation and promoted atheroselerosis development. The foam cell formation induced by berberinc was also observed in mouse RAW264.7 cells, as well as in mouse and human primary macrophages. By inducing scavenger receptor A （SR-A） expression in macrophages, berberine increased the uptake of modified LDL （DiO-Ac-LDL）. Bcrberine-induced SR-A expression was also observed in macrophage foam cells in vivo and in the cells at atherosclerotic lesion. Analysis in RAW264.7 cells indicated that berberine induced SR-A expression by suppressing PTEN expression, which led to sustained Akt activation. Our results suggest that to evaluate the potential of a cholesterol-reducing compound in alleviating atherosclerosis, its effect on the ceils involved in atherosclerosis development, such as macrophages, should also be considered. Promotion of foam cell formation could counter-balance the beneficial effect of lowering serum cholesterol.展开更多
基金supported by the Natural Science Foundation of China(Grant Nos.81070248,81070249,31171132,and 81100612).
文摘Atherosclerosis is a chronic,inflammatory disorder characterized by the deposition of excess lipids in the arterial intima.The formation of macrophage-derived foam cells in a plaque is a hallmark of the development of atherosclerosis.Lipid homeostasis,especially cho-lesterol homeostasis,plays a crucial role during the formation of foam cells.Recently,lipid droplet-associated proteins,including PAT and CIDE family proteins,have been shown to control the development of athero-sclerosis by regulating the formation,growth,stabiliza-tion and functions of lipid droplets in macrophage-derived foam cells.This review focuses on the potential mechanisms of formation of macrophage-derived foam cells in atherosclerosis with particular emphasis on the role of lipid homeostasis and lipid droplet-associated proteins.Understanding the process of foam cell for-mation will aid in the future discovery of novel thera-peutic interventions for atherosclerosis.
文摘Berberine is identified to lower the serum cholesterol level in human and hamster through the induction of low density lipoproteins （LDL） receptor in hepatic cells. To evaluate its potential in preventing atherosclerosis, the effect of berberine on atherosclerosis development in apolipoprotcin E-deficient （apoE^-/-） mice was investigated. In apoE^-/- mice, berberine induced in rivo foam cell formation and promoted atheroselerosis development. The foam cell formation induced by berberinc was also observed in mouse RAW264.7 cells, as well as in mouse and human primary macrophages. By inducing scavenger receptor A （SR-A） expression in macrophages, berberine increased the uptake of modified LDL （DiO-Ac-LDL）. Bcrberine-induced SR-A expression was also observed in macrophage foam cells in vivo and in the cells at atherosclerotic lesion. Analysis in RAW264.7 cells indicated that berberine induced SR-A expression by suppressing PTEN expression, which led to sustained Akt activation. Our results suggest that to evaluate the potential of a cholesterol-reducing compound in alleviating atherosclerosis, its effect on the ceils involved in atherosclerosis development, such as macrophages, should also be considered. Promotion of foam cell formation could counter-balance the beneficial effect of lowering serum cholesterol.
