ATP-binding cassette A1 protein and HDL homeostasis.
For three decades, low-density lipoprotein (LDL) dominated research into cholesterol metabolism and atherosclerosis, whereas scant attention was paid to high-density lipoprotein (HDL), an equally important risk factor for cardiovascular disease. This low interest reflected the lack of knowledge about physiological HDL receptors. As a result, our understanding of HDL-cell interactions failed to develop alongside that of LDL, and mechanisms through which atheroprotective HDL promoted clearance of cholesterol from peripheral cells remained poorly-defined. Interest was kindled with the recognition that scavenger receptor class B, type I is the cell-surface protein in hepatocytes and steroidogenic tissues which selectively extracts cholesteryl esters from HDL. Greater impetus still was given by the discovery that mutations in the gene encoding the ATP-binding cassette transporter, class A1 (ABCA1) are the cause of Tangier disease, a rare recessive disorder with near-absent plasma HDL. The ABCA1 transmembrane protein is crucial for efficient efflux of cellular cholesterol and HDL maturation and has emerged as a promising therapeutic target for cardiovascular disease. The hope is that new drugs, regulating ABCA1 activity and HDL homeostasis, will accelerate cholesterol efflux from lipid-laden foam cells and thus promote regression of atherosclerotic lesions.
Owen
James S
JS
Department of Medicine, Royal Free and University College Medical School, Royal Free Campus, London NW3 2PF, UK. j.owen@rfc.ucl.ac.uk
Mulcahy
Jane V
JV
D018528:ATP-Binding Cassette Transporters / Q000502:physiology*; D001161:Arteriosclerosis / Q000209:etiology* / Q000503:physiopathology*; D004268:DNA-Binding Proteins / Q000502:physiology*; D006706:Homeostasis / Q000502:physiology*; D006801:Humans; D008075:Lipoproteins, HDL / Q000502:physiology*; D051818:Replication Protein C; D012307:Risk Factors
D018528:ATP-Binding Cassette Transporters; D004268:DNA-Binding Proteins; D008075:Lipoproteins, HDL; D051818:Replication Protein C