Scavenger receptor type BI potentiates reverse cholesterol transport system by removing cholesterol ester from HDL.
High-density lipoprotein (HDL) plays an important role in reverse cholesterol transport by removing accumulated cholesterol from extrahepatic tissues. Subsequently, cholesterol ester (CE) on HDL in humans is transported to apolipoprotein B-containing lipoproteins by cholesteryl ester transfer protein (CETP). CETP deficiency, which is common in the Japanese population, leads to a marked increase in HDL-cholesterol levels due to impaired CE transport from HDL to LDL. It has been reported that the HDL observed in CETP deficiency is an atherogenic lipoprotein, as it contains a large amount of CE. Scavenger receptor class B type I (SR-BI) has been found to be an authentic HDL receptor that mediates the selective uptake of HDL CE and the bi-directional transfer of free cholesterol between HDL and cells. In the present study, the interaction between SR-BI and CE-rich HDL from CETP-deficient patient was studied in order to evaluate the anti-atherosclerotic role of SR-BI in relation to CE uptake and reverse cholesterol transport. When CE-rich HDL was added to the medium of SR-BI-transfected CHO (SR-BI CHO) cells, more CE accumulated in SR-BI CHO cells compared to control HDL. In contrast, the amount of cholesterol efflux from SR-BI CHO cells into HDL was almost the same between the two HDLs. Therefore, when CE-rich HDL was added to the medium of SR-BI CHO cells, the intracellular CE content increased significantly. Moreover, the particle size of HDL in CETP-deficient patient decreased significantly when the HDL was added to the medium of SR-BI CHO cells, and this HDL showed an increment of CE efflux from foam cells. These results indicate that SR-BI reduces the cholesterol content and size of the CE-rich HDL from CETP deficiency, which ultimately activate reverse cholesterol transport system.
Kinoshita
Makoto
M
Department of Internal Medicine, Teikyo University School of Medicine, 2-11-1 Kaga, Itabashi, Tokyo 173-8605, Japan. makkino@med.teikyo-u.ac.jp
Fujita
Mineko
M
Usui
Shinichi
S
Maeda
Yoko
Y
Kudo
Mikiko
M
Hirota
Daisuke
D
Suda
Takaoki
T
Taki
Masanari
M
Okazaki
Mitsuyo
M
Teramoto
Tamio
T
D000818:Animals; D001161:Arteriosclerosis / Q000473:pathology / Q000503:physiopathology*; D001693:Biological Transport, Active / Q000187:drug effects*; D018955:CD36 Antigens; D016466:CHO Cells; D002352:Carrier Proteins; D002478:Cells, Cultured; D002784:Cholesterol / Q000378:metabolism; D053480:Cholesterol Ester Transfer Proteins; D002788:Cholesterol Esters / Q000378:metabolism*; D006224:Cricetinae; D003412:Cricetulus; D006023:Glycoproteins / Q000172:deficiency*; D006801:Humans; D008075:Lipoproteins, HDL / Q000187:drug effects / Q000378:metabolism*; D011336:Probability; D011971:Receptors, Immunologic; D051116:Receptors, Scavenger; D012016:Reference Values; D012494:Sampling Studies; D051122:Scavenger Receptors, Class B; D012680:Sensitivity and Specificity; D013045:Species Specificity
D018955:CD36 Antigens; C506642:CETP protein, human; D002352:Carrier Proteins; D053480:Cholesterol Ester Transfer Proteins; D002788:Cholesterol Esters; D006023:Glycoproteins; D008075:Lipoproteins, HDL; D011971:Receptors, Immunologic; D051116:Receptors, Scavenger; C495124:SCARB1 protein, human; D051122:Scavenger Receptors, Class B; D002784:Cholesterol