Receptors and lipid transfer proteins in HDL metabolism.
It is believed that HDL exerts its anti-atherogenic effects through the process of delivering cholesterol from peripheral tissues back to the liver for removal from the body (i.e., reverse cholesterol transport). The metabolic life cycle of HDL lipid and apolipoproteins during reverse cholesterol transport involves both its modification in plasma by lipid transfer proteins and the clearance from plasma of HDL lipid and protein mediated by hepatic cell surface proteins. We review recent work from our laboratory that focuses on specific metabolic steps in reverse cholesterol transport and the results of altering these steps on plasma HDL levels and atherosclerosis. Recently, SR-BI was shown to be an authentic HDL receptor mediating the selective uptake of HDL lipids into cells without degradation of HDL proteins. We discuss the evidence for additional receptor activity mediating HDL protein catabolism in the liver from studies in obese (ob/ob) mice, which have markedly increased HDL due to a defect in hepatic catabolism of apoA-I and apoA-II. In addition, we review recent findings that phospholipid transfer protein deficiency in mice results in markedly reduced HDL levels. Lastly, we highlight our findings that overexpression of SR-BI in LDL receptor-deficient mice results in decreased atherosclerosis.
Silver
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Department of Medicine, Columbia University, New York, New York 10032, USA. dls51@columbia.edu
Jiang
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Arai
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Bruce
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Tall
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D000818:Animals; D016632:Apolipoprotein A-I / Q000378:metabolism; D016633:Apolipoprotein A-II / Q000378:metabolism; D001161:Arteriosclerosis / Q000097:blood / Q000235:genetics / Q000503:physiopathology*; D018955:CD36 Antigens / Q000235:genetics / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism*; D006801:Humans; D008075:Lipoproteins, HDL / Q000378:metabolism*; D008099:Liver / Q000378:metabolism; D008565:Membrane Proteins; D051379:Mice; D011971:Receptors, Immunologic; D011973:Receptors, LDL / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D018110:Receptors, Lipoprotein / Q000235:genetics / Q000378:metabolism; D051116:Receptors, Scavenger; D051122:Scavenger Receptors, Class B
D016632:Apolipoprotein A-I; D016633:Apolipoprotein A-II; D018955:CD36 Antigens; D002352:Carrier Proteins; D008075:Lipoproteins, HDL; D008565:Membrane Proteins; D011971:Receptors, Immunologic; D011973:Receptors, LDL; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; C454739:Scarb1 protein, mouse; D051122:Scavenger Receptors, Class B; C030363:lipid transfer protein