Molecular interaction between caveolin-1 and ABCA1 on high-density lipoprotein-mediated cholesterol efflux in aortic endothelial cells.
OBJECTIVE
Caveolin-1 and ATP-binding cassette transporter A1 (ABCA1) are proteins that are involved in cellular cholesterol efflux. In this study, we analyzed the relationships between caveolin-1 and ABCA1 on high-density lipoprotein (HDL)-mediated cholesterol efflux in rat aortic endothelial cells.


RESULTS
Overexpression of caveolin-1 by transfection with caveolin-1 cDNA in aortic endothelial cells up-regulated ABCA1 expression and enhanced cholesterol efflux. Suppression of caveolin-1 by siRNA decreased ABCA1 expression and reduced cholesterol efflux. The number of caveolae increased after transfection with caveolin-1 into cells. Immunoprecipitation assays revealed a molecular interaction between caveolin-1 and ABCA1 in the plasma membrane and in the cytoplasm after HDL incubation. Immunoelectron microscopy demonstrated that caveolin-1 colocalized with ABCA1 in the caveolae and in the cytoplasmic vesicles; it was also found that caveolin-1 and ABCA1 colocalized with cellular cholesterol by immunofluorescence microscopy. Blocking of intracellular lipid transport by inhibitors disrupted the interaction between caveolin-1 and ABCA1 and reduced cholesterol to methyl-beta-cyclodextrin and HDL.


CONCLUSIONS
The molecular interaction between caveolin-1 and ABCA1 is associated with the HDL-mediated cholesterol efflux pathway in aortic endothelial cells.
Lin
Yu-Chun
YC
Department of Life Science, Tunghai University, Taichung, Taiwan, ROC.
Ma
Chang
C
Hsu
Wei-Ching
WC
Lo
Hsiao-Fan
HF
Yang
Vivian C
VC
D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters / Q000032:analysis / Q000378:metabolism*; D000818:Animals; D001011:Aorta; D001692:Biological Transport; D051242:Caveolin 1 / Q000032:analysis / Q000378:metabolism*; D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism; D002478:Cells, Cultured; D002784:Cholesterol / Q000378:metabolism* / Q000494:pharmacology; D003593:Cytoplasm / Q000737:chemistry / Q000378:metabolism; D042783:Endothelial Cells / Q000737:chemistry / Q000378:metabolism*; D005786:Gene Expression Regulation; D015151:Immunoblotting / Q000379:methods; D008075:Lipoproteins, HDL / Q000378:metabolism* / Q000494:pharmacology; D008856:Microscopy, Fluorescence; D016253:Microscopy, Immunoelectron; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014161:Transduction, Genetic / Q000379:methods
D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters; D051242:Caveolin 1; D008075:Lipoproteins, HDL; D034741:RNA, Small Interfering; D002784:Cholesterol