Cellular physiology of cholesterol efflux in vascular endothelial cells

• Published in: Circulation (New York, N.Y.) N.Y.), 2004-11, Vol.110 (18), p.2881-2888
• Main Authors: O'Connell, Brian J, Denis, Maxime, Genest, Jacques
• Format: Article
• Language: English
• Subjects: 8-Bromo Cyclic Adenosine Monophosphate - pharmacology; Animals; Aorta; Apolipoprotein A-I - pharmacology; ATP Binding Cassette Transporter 1; ATP Binding Cassette Transporter, Sub-Family G, Member 1; ATP-Binding Cassette Transporters - antagonists & inhibitors; ATP-Binding Cassette Transporters - genetics; ATP-Binding Cassette Transporters - metabolism; Cattle; CD36 Antigens; Cells, Cultured - drug effects; Cells, Cultured - metabolism; Cercopithecus aethiops; Cholesterol - metabolism; Cholesterol - pharmacology; COS Cells; Endothelial Cells - drug effects; Endothelial Cells - metabolism; Endothelium, Vascular - cytology; Endothelium, Vascular - physiology; Fibroblasts - drug effects; Fibroblasts - metabolism; Fibroblasts - pathology; Gene Expression Profiling; Gene Expression Regulation - drug effects; Glyburide - pharmacology; Humans; Hydroxycholesterols - pharmacology; Lipoproteins, HDL - pharmacology; Lipoproteins, HDL3; Oligonucleotide Array Sequence Analysis; Receptors, Immunologic - antagonists & inhibitors; Receptors, Immunologic - genetics; Receptors, Immunologic - metabolism; Receptors, Scavenger; Recombinant Fusion Proteins - physiology; Serum Albumin, Bovine - pharmacology; Tangier Disease - genetics; Tangier Disease - pathology; Transfection; Umbilical Veins
• ISSN: 0009-7322; 1524-4539
• DOI: 10.1161/01.CIR.0000146333.20727.2B

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. 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. Endothelial cells may use nontraditional pathways for cholesterol efflux.