Cellular physiology of cholesterol efflux in vascular endothelial cells.
BACKGROUND
Of the cells that compose the atherosclerotic plaque, vascular endothelial cells are the most resistant to cholesterol accumulation. Cholesterol efflux pathways may play an important role in endothelial cholesterol homeostasis.


RESULTS
We examined the global genetic response of endothelial cells to cholesterol and in particular the contribution of the cholesterol efflux proteins ATP-binding cassette transporter A1 (ABCA1), ATP-binding cassette transporter G1 (ABCG1), and scavenger receptor B-I (SR-BI) to endothelial cell cholesterol efflux. The ABCG1 gene is induced in endothelial cells by cholesterol, whereas ABCA1 is not. Using specific chemical inhibitors of ABC transporters and SR-BI, we have shown that neither ABC transporters nor SR-BI is required for apolipoprotein A-1-mediated endothelial cholesterol efflux.


CONCLUSIONS
Endothelial cells may use nontraditional pathways for cholesterol efflux.
O'Connell
Brian J
BJ
Cardiovascular Genetics Laboratory, McGill University Health Centre, Royal Victoria Hospital, Montreal, Quebec, Canada.
Denis
Maxime
M
Genest
Jacques
J
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D064286:ATP Binding Cassette Transporter 1; D000070998:ATP Binding Cassette Transporter, Subfamily G, Member 1; D018528:ATP-Binding Cassette Transporters / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001011:Aorta; D016632:Apolipoprotein A-I / Q000494:pharmacology; D018955:CD36 Antigens; D019556:COS Cells; D002417:Cattle; D002478:Cells, Cultured / Q000187:drug effects / Q000378:metabolism; D002522:Chlorocebus aethiops; D002784:Cholesterol / Q000378:metabolism* / Q000494:pharmacology; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000166:cytology / Q000502:physiology*; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects; D005905:Glyburide / Q000494:pharmacology; D006801:Humans; D006888:Hydroxycholesterols / Q000494:pharmacology; D008075:Lipoproteins, HDL / Q000494:pharmacology; D053440:Lipoproteins, HDL3; D020411:Oligonucleotide Array Sequence Analysis; D011971:Receptors, Immunologic / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D051116:Receptors, Scavenger; D011993:Recombinant Fusion Proteins / Q000502:physiology; D012710:Serum Albumin, Bovine / Q000494:pharmacology; D013631:Tangier Disease / Q000235:genetics / Q000473:pathology; D014162:Transfection; D014471:Umbilical Veins
C577836:ABCA1 protein, human; C419353:ABCG1 protein, human; D064286:ATP Binding Cassette Transporter 1; D000070998:ATP Binding Cassette Transporter, Subfamily G, Member 1; D018528:ATP-Binding Cassette Transporters; D016632:Apolipoprotein A-I; D018955:CD36 Antigens; D006888:Hydroxycholesterols; D008075:Lipoproteins, HDL; D053440:Lipoproteins, HDL3; D011971:Receptors, Immunologic; D051116:Receptors, Scavenger; D011993:Recombinant Fusion Proteins; C003585:22-hydroxycholesterol; D015124:8-Bromo Cyclic Adenosine Monophosphate; D012710:Serum Albumin, Bovine; D002784:Cholesterol; D005905:Glyburide