A novel model of cholesterol efflux from Iipid-loaded cells  

作　　者：Di-xian LUO De-liang CAO Yan XIONG Xu-hong PENG Duan-fang LIAO 

机构地区：[1]Department of Pharmacology, School of Pharmaceutics, Central South University, Changsha 410083, China [2]Institute of Pharmacy & Pharmacology, Life Science Research Center, University of South China, Hengyang 421001, China [3]First People's Hospital of Chenzhou, Chenzhou 423000, China [4]Department of Microbiology, Immunology and Cell Biology, Southern Illinois University School of Medicine, Springfield IL 62702, USA [5]Department of Traditional Chinese Diagnotics, School of Pharmacy, Hunan University of Chinese Medicine, Changsha 420108, China

出　　处：《Acta Pharmacologica Sinica》2010年第10期1243-1257,共15页中国药理学报（英文版）

基　　金：Acknowledgements This work was supported by the National Natural Science Foundation of China （30770868, 30971170）, the Natural Science Foundation of Hunan Province, China （No 06JJ5055） and the Science ＆ Technology Department of Hunan Province （No 04FJ4064）. The authors acknowledge and express appreciation to Rhona KELLY for editing the manuscript.

摘　　要：Cholesterol efflux from lipid-loaded cells is a key athero-protective event that counteracts cholesterol uptake. The imbalance between cholesterol efflux and uptake determines the prevention or development of atherosclerosis. Many proteins and factors participate in the cholesterol efflux event. However, there are currently no systematic models of reverse cholesterol transport （RCT） that include most RCT-related factors and events. On the basis of recent research findings from other and our laboratories, we propose a novel model of one center and four systems with coupling transportation and networking regulation. This model represents a common way of cholesterol efflux; however, the systems in the model consist of different proteins/factors in different cells. In this review, we evaluate the novel model in vascular smooth muscle cells （VSMCs） and macrophages, which are the most important original cells of foam cells. This novel model consists of 1） a caveolae transport center, 2） an intracellular trafficking system of the caveolin-1 complex, 3） a transmembrane transport system of the ABC-A1 complex, 4） a transmembrane transport system of the SR-B1 complex, and 5） an extracelluar trafficking system of HDL/Apo-AI. In brief, the caveolin-1 system transports cholesterol from intracellular compartments to caveolae. Subsequently, both ABC-A1 and SR-B1 complex systems transfer cholesterol from caveolae to extracellular HDL/Apo-AI. The four systems are linked by a regulatory network. This model provides a simple and concise way to understand the dynamic pro- cess of atherosclerosis.Cholesterol efflux from lipid-loaded cells is a key athero-protective event that counteracts cholesterol uptake. The imbalance between cholesterol efflux and uptake determines the prevention or development of atherosclerosis. Many proteins and factors participate in the cholesterol efflux event. However, there are currently no systematic models of reverse cholesterol transport （RCT） that include most RCT-related factors and events. On the basis of recent research findings from other and our laboratories, we propose a novel model of one center and four systems with coupling transportation and networking regulation. This model represents a common way of cholesterol efflux; however, the systems in the model consist of different proteins/factors in different cells. In this review, we evaluate the novel model in vascular smooth muscle cells （VSMCs） and macrophages, which are the most important original cells of foam cells. This novel model consists of 1） a caveolae transport center, 2） an intracellular trafficking system of the caveolin-1 complex, 3） a transmembrane transport system of the ABC-A1 complex, 4） a transmembrane transport system of the SR-B1 complex, and 5） an extracelluar trafficking system of HDL/Apo-AI. In brief, the caveolin-1 system transports cholesterol from intracellular compartments to caveolae. Subsequently, both ABC-A1 and SR-B1 complex systems transfer cholesterol from caveolae to extracellular HDL/Apo-AI. The four systems are linked by a regulatory network. This model provides a simple and concise way to understand the dynamic pro- cess of atherosclerosis.

关 键 词：ATHEROSCLEROSIS lipid-loaded cells cholesterol effiux CAVEOLAE CAVEOLIN-1 ABC-A1 SR-B1 HDL Apo-A1 

分 类 号：Q591.5[生物学—生物化学] S852.4[农业科学—基础兽医学]