Research Topics
Genomes and Genes | John OramSummaryAffiliation: University of Washington Country: USA Publications
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Publications
ATP-binding cassette transporter A1 mediates cellular secretion of alpha-tocopherolJ F Oram
Department of Medicine, University of Washington, Seattle, WA 98195, USA
J Biol Chem 276:39898-902. 2001..These studies provide evidence that ABCA1 mediates secretion of cellular alpha-TOH into the HDL metabolic pathway, a process that may facilitate vitamin transport between tissues and influence lipid oxidation...- Molecular basis of cholesterol homeostasis: lessons from Tangier disease and ABCA1John F Oram
Department of Medicine, Box 356426, University of Washington, Seattle, WA 98195 6426, USA
Trends Mol Med 8:168-73. 2002..Because of its ability to deplete macrophages of cholesterol and to raise plasma HDL levels, ABCA1 has become a promising therapeutic target for preventing cardiovascular disease... - The cholesterol mobilizing transporter ABCA1 as a new therapeutic target for cardiovascular diseaseJohn F Oram
Department of Medicine, University of Washington, Seattle, WA 98195 6426, USA
Trends Cardiovasc Med 12:170-5. 2002..This makes ABCA1 a promising new therapeutic target for reducing cholesterol deposits in tissues, eliminating excess cholesterol from the body, and preventing cardiovascular disease... - ATP-binding cassette transporter A1 and cholesterol traffickingJohn F Oram
Department of Medicine, University of Washington, Seattle 98195 6426, USA
Curr Opin Lipidol 13:373-81. 2002..The present review summarizes the more recent of those studies and evaluates their implications for the role of ABCA1 in cholesterol transport, HDL metabolism, and atherogenesis... - HDL apolipoproteins and ABCA1: partners in the removal of excess cellular cholesterolJohn F Oram
Department of Medicine, Box 356426, University of Washington, Seattle, WA 98195, USA
Arterioscler Thromb Vasc Biol 23:720-7. 2003..These findings implicate the apolipoprotein/ABCA1 pathway as an important therapeutic target for treating cardiovascular disease... 
An amphipathic helical region of the N-terminal barrel of phospholipid transfer protein is critical for ABCA1-dependent cholesterol effluxJohn F Oram
Division of Metabolism, Endocrinology and Nutrition, Department of Medicine, Box 356426, University of Washington, Seattle, Washington 98195, USA
J Biol Chem 283:11541-9. 2008..Direct interactions with ABCA1 and activation of signaling pathways likely involve other structural determinants of PLTP...- Phospholipid transfer protein interacts with and stabilizes ATP-binding cassette transporter A1 and enhances cholesterol efflux from cellsJohn F Oram
Department of Medicine, University of Washington, Seattle, Washington 98195 6426, USA
J Biol Chem 278:52379-85. 2003..Thus, PLTP mimics apolipoproteins in removing cellular lipids by the ABCA1 pathway, except that PLTP acts more as an intermediary in the transfer of cellular lipids to lipoprotein particles... - ATP-Binding cassette cholesterol transporters and cardiovascular diseaseJohn F Oram
Department of Medicine, Box 356426, University of Washington, Seattle, WA 98195 6426, USA
Circ Res 99:1031-43. 2006..Their beneficial effects on cholesterol homeostasis have made these transporters important new therapeutic targets for preventing and reversing CVD... - When good cholesterol turns bad: the evolving saga of CETP inhibitors and clinical strategies to elevate high-density lipoproteinJohn F Oram
Department of Medicine, Box 356426, University of Washington, 1959 NE Pacific Street, Seattle, WA 98195-6426, USA
Curr Diab Rep 8:165-7. 2008 - ATP-binding cassette transporter A1: a cell cholesterol exporter that protects against cardiovascular diseaseJohn F Oram
Department of Medicine, University of Washington, Seattle, WA 98195 6426, USA
Physiol Rev 85:1343-72. 2005..The ABCA1 pathway has therefore become an important new therapeutic target for treating cardiovascular disease... - The ins and outs of ABCAJohn F Oram
Department of Medicine, University of Washington, Seattle, WA, USA
J Lipid Res 49:1150-1. 2008 - When good cholesterol turns bad: the evolving saga of CETP inhibitors and clinical strategies to elevate high-density lipoproteinJohn F Oram
Department of Medicine, Box 356426, University of Washington, 1959 NE Pacific Street, Seattle, WA 98195-6426, USA
Curr Atheroscler Rep 9:425-7. 2007 - ABCA1-mediated transport of cellular cholesterol and phospholipids to HDL apolipoproteinsJ F Oram
Department of Medicine, University of Washington, Seattle 98195, USA
Curr Opin Lipidol 11:253-60. 2000..Thus, the ABCA1 pathway has become an important therapeutic target for mobilizing excess cholesterol from tissue macrophages and protecting against atherosclerosis... - ABCA1. The gatekeeper for eliminating excess tissue cholesterolJ F Oram
Department of Medicine, Box 356426, 1959 NE Pacific Pl, University of Washington, Seattle, WA 98195 6426, USA
J Lipid Res 42:1173-9. 2001..Therefore, as the primary gatekeeper for eliminating tissue cholesterol, ABCA1 has a major impact on cellular and whole body cholesterol metabolism and is likely to play an important role in protecting against cardiovascular disease... - Novel approaches to treating cardiovascular disease: lessons from Tangier diseaseJ F Oram
University of Washington, Department of Medicine, Seattle, Washington, WA 98195 6426, USA
Expert Opin Investig Drugs 10:427-38. 2001..By reducing plaque formation and rupture independently of the atherogenic factors involved, these drugs would be powerful agents for treating CVD... - Tangier disease and ABCA1J F Oram
University of Washington, Division of Metabolism, Endocrinology and Nutrition, Box 356426, Seattle, WA 98195 6426, USA
Biochim Biophys Acta 1529:321-30. 2000.... - ABCA1 is the cAMP-inducible apolipoprotein receptor that mediates cholesterol secretion from macrophagesJ F Oram
Department of Medicine, University of Washington, Seattle, Washington 98195, USA
J Biol Chem 275:34508-11. 2000..Thus, ABCA1 is likely to be the cAMP-inducible apolipoprotein receptor that promotes removal of cholesterol and phospholipids from macrophages... - Sterol efflux mediated by endogenous macrophage ApoE expression is independent of ABCA1Z H Huang
Department of Medicine, Rush-Presbyterian-St. Luke's Medical Center, Chicago, IL 60612, USA
Arterioscler Thromb Vasc Biol 21:2019-25. 2001..The results of these studies indicate that the increment in sterol efflux mediated by the endogenous expression of apoE in macrophages does not depend on ABCA1 expression or activity... - Cyclic AMP stimulates efflux of intracellular sterol from cholesterol-loaded cellsB M Hokland
Department of Medicine, University of Washington, Seattle 98195
J Biol Chem 268:25343-9. 1993..Thus, at least two distinct protein kinase signalling pathways modulate transport of intracellular sterols in cholesterol-loaded cells... - Cellular localization and characterization of proteins that bind high density lipoproteinB Hokland
Department of Medicine, University of Washington, Seattle 98195
J Lipid Res 33:1335-42. 1992..The cellular localization and physical properties of the 110 and 130 kDa proteins suggest that they may play a role in binding of HDL to the cell surface... - Mapping of the gene for high-density lipoprotein binding protein (Hdlbp) to proximal mouse chromosome 1R C LeBoeuf
Department of Medicine, University of Washington, Seattle 98195
Genomics 23:296-8. 1994 - High density lipoprotein stimulates sterol translocation between intracellular and plasma membrane pools in human monocyte-derived macrophagesM Aviram
Department of Medicine, University of Washington, Seattle 98195
J Lipid Res 30:65-76. 1989..However, in nonloaded macrophages, HDL stimulates sterol movement from the plasma membrane into intracellular pools by a receptor-independent process... - Myeloperoxidase and inflammatory proteins: pathways for generating dysfunctional high-density lipoprotein in humansTomas Vaisar
Department of Medicine, HSB BB512, Box 356426, University of Washington, 1959 NE Pacific Street, Seattle, WA 98195, USA
Curr Atheroscler Rep 9:417-24. 2007..Thus, oxidative modifications to HDL and changes in its protein composition might be useful biomarkers-and perhaps mediators-of CVD... - Unsaturated fatty acids phosphorylate and destabilize ABCA1 through a phospholipase D2 pathwayYutong Wang
Department of Medicine, University of Washington, Seattle, Washington 98195, USA
J Biol Chem 280:35896-903. 2005..These data provide evidence that intracellular unsaturated acyl-CoA derivatives destabilize ABCA1 by activating a PLD2 signaling pathway... - Acrolein impairs ATP binding cassette transporter A1-dependent cholesterol export from cells through site-specific modification of apolipoprotein A-IBaohai Shao
Department of Medicine, University of Washington, Seattle, Washington 98195, USA
J Biol Chem 280:36386-96. 2005..Thus, acrolein might contribute to atherogenesis by impairing cholesterol removal from the artery wall... - Janus kinase 2 modulates the lipid-removing but not protein-stabilizing interactions of amphipathic helices with ABCA1Chongren Tang
Division of Metabolism, Endocrinology, and Nutrition, University of Alabama at Birmingham Medical Center, Birmingham, AL 35294, USA
J Lipid Res 47:107-14. 2006..These findings show that amphipathic helices coordinate the activity of ABCA1 by several distinct mechanisms that are likely to involve different cell surface binding sites... - Myeloperoxidase: an inflammatory enzyme for generating dysfunctional high density lipoproteinBaohai Shao
Department of Medicine, University of Washington, Seattle, 98195, USA
Curr Opin Cardiol 21:322-8. 2006..Moreover, oxidized HDL might prove useful as a blood marker for clinically significant cardiovascular disease in humans... - Pathways for oxidation of high-density lipoprotein in human cardiovascular diseaseBaohai Shao
Department of Medicine, University of Washington, Seattle, WA 98195, USA
Curr Opin Mol Ther 8:198-205. 2006..Collectively, these observations indicate that MPO oxidatively damages HDL in humans and suggest that oxidation of specific amino acid residues in apoA-I may contribute to atherogenesis by impairing cholesterol efflux from macrophages... - ABCA1 and ABCG1 or ABCG4 act sequentially to remove cellular cholesterol and generate cholesterol-rich HDLAshley M Vaughan
Department of Medicine, Division of Metabolism, Endocrinology, and Nutrition, University of Washington, Seattle, WA 98195 6426, USA
J Lipid Res 47:2433-43. 2006..These results suggest that ABCG1 and ABCG4 act in concert with ABCA1 to maximize the removal of excess cholesterol from cells and to generate cholesterol-rich lipoprotein particles... - Myeloperoxidase impairs ABCA1-dependent cholesterol efflux through methionine oxidation and site-specific tyrosine chlorination of apolipoprotein A-IBaohai Shao
Department of Medicine, University of Washington, Seattle, Washington 98195, USA
J Biol Chem 281:9001-4. 2006.... - Ethanol induces cholesterol efflux and up-regulates ATP-binding cassette cholesterol transporters in fetal astrocytesMarina Guizzetti
Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, Washington 98105, USA
J Biol Chem 282:18740-9. 2007..Ethanol did not affect cholesterol synthesis and reduced the levels of intracellular cholesterol in rat astrocytes. Retinoic acid, which induces teratogenic effects similarly to ethanol, also caused up-regulation of ABCA1 and ABCG1... - Acrolein modifies apolipoprotein A-I in the human artery wallBaohai Shao
Division of Metabolism, Endocrinology and Nutrition, Box 356426, University of Washington, Seattle, WA 98195
Ann N Y Acad Sci 1043:396-403. 2005..Our observations suggest that acrolein may interfere with normal HDL cholesterol transport by modifying apoA-I. This structural damage might play a critical role in atherogenesis by impairing cholesterol removal from artery wall cells... - ABCG1 redistributes cell cholesterol to domains removable by high density lipoprotein but not by lipid-depleted apolipoproteinsAshley M Vaughan
Department of Medicine, Division of Metabolism, Endocrinology and Nutrition, University of Washington, Seattle, Washington 98195 6426, USA
J Biol Chem 280:30150-7. 2005..These studies show that ABCG1 redistributes cholesterol to cell-surface domains where it becomes accessible for removal by HDL, consistent with a direct role of ABCG1 in cellular cholesterol transport... - Unsaturated fatty acids inhibit cholesterol efflux from macrophages by increasing degradation of ATP-binding cassette transporter A1Yutong Wang
Department of Medicine, University of Washington, Seattle, Washington 98195, USA
J Biol Chem 277:5692-7. 2002..These findings raise the possibility that an increased supply of unsaturated fatty acids in the artery wall promotes atherogenesis by impairing the ABCA1 cholesterol secretory pathway in macrophages... - Polarized cholesterol and phospholipid efflux in cultured gall-bladder epithelial cells: evidence for an ABCA1-mediated pathwayJin Lee
Division of Gastroenterology, Box 356424, University of Washington, 1959 NE Pacific Street, Seattle, WA 98195, USA
Biochem J 364:475-84. 2002..This efflux pathway is stimulated by cAMP and by LXRalpha/RXR ligands, and in the case of the cAMP pathway appears to involve a role for biliary apoA-I... - ABCA1 redistributes membrane cholesterol independent of apolipoprotein interactionsAshley M Vaughan
Department of Medicine, University of Washington, Seattle, WA 98195-6426, USA
J Lipid Res 44:1373-80. 2003..These studies show that ABCA1 redistributes cholesterol to cell-surface domains, where it becomes accessible for removal by apolipoproteins, consistent with a direct role of ABCA1 in cholesterol transport... - Cultured gallbladder epithelial cells synthesize apolipoproteins A-I and EJin Lee
Division of Gastroenterology, University of Washington, Seattle, WA 98195, USA
Am J Physiol Gastrointest Liver Physiol 285:G630-41. 2003..Therefore, GBEC synthesize apoA-I and -E and efflux cholesterol using ABCA1- and non-ABCA1- mediated pathways. These processes may alter gallbladder biliary cholesterol concentrations and thereby influence gallstone formation... - Lipoprotein lipase and hepatic lipase: their relationship with HDL subspecies Lp(A-I) and Lp(A-I,A-II)Marian C Cheung
Department of Medicine, University of Washington, Seattle, WA 98103, USA
J Lipid Res 44:1552-8. 2003..Furthermore, select correlations of LPL and/or HL with the apoA-I, cholesterol, and triglyceride of Lp(A-I) but not Lp(A-I,A-II) imply that the apoA-I and lipid of Lp(A-I) and Lp(A-I,A-II) are not fully equilibrated... - Janus kinase 2 modulates the apolipoprotein interactions with ABCA1 required for removing cellular cholesterolChongren Tang
Department of Medicine, University of Washington, Seattle, Washington 98195 6426, USA
J Biol Chem 279:7622-8. 2004..These results suggest that the interaction of apolipoproteins with ABCA1-expressing cells activates JAK2, which in turn activates a process that enhances apolipoprotein interactions with ABCA1 and lipid removal from cells... - LXR-mediated activation of macrophage stearoyl-CoA desaturase generates unsaturated fatty acids that destabilize ABCA1Yutong Wang
Department of Medicine, University of Washington, Seattle, WA 98195, USA
J Lipid Res 45:972-80. 2004..Thus, with cholesterol-loaded macrophages exposed to saturated fatty acids, activated LXR/RXR may counteract the enhanced ABCA1 transcription by reducing the ABCA1 protein content... - Identification of an apolipoprotein A-I structural element that mediates cellular cholesterol efflux and stabilizes ATP binding cassette transporter A1Pradeep Natarajan
Lawrence Berkeley National Laboratory, Donner Laboratory MS1 224, University of California at Berkeley, California 94720, USA
J Biol Chem 279:24044-52. 2004..These results suggest that a specific structural element possessing a linear array of acidic residues spanning two apoA-I amphipathic alpha-helices is required to mediate cholesterol efflux and stabilize ABCA1... - Advanced glycation end product precursors impair ABCA1-dependent cholesterol removal from cellsMarisa Passarelli
Department of Medicine, Box 356426, University of Washington, Seattle, WA 98195 6426, USA
Diabetes 54:2198-205. 2005.... - Thematic review series: The immune system and atherogenesis. Lipoprotein-associated inflammatory proteins: markers or mediators of cardiovascular disease?Alan Chait
Division of Metabolism, Endocrinology, and Nutrition, Department of Medicine, University of Washington, Seattle, WA 98195, USA
J Lipid Res 46:389-403. 2005..In future studies, it will be important to determine whether these proteins play a causal role in atherogenesis... - Tyrosine 192 in apolipoprotein A-I is the major site of nitration and chlorination by myeloperoxidase, but only chlorination markedly impairs ABCA1-dependent cholesterol transportBaohai Shao
Department of Medicine, University of Washington, Seattle, WA 98195, USA
J Biol Chem 280:5983-93. 2005..This impaired biological activity of chlorinated apoA-I suggests that MPO-mediated oxidation of HDL might contribute to the link between inflammation and cardiovascular disease... - Direct effects of long-chain non-esterified fatty acids on vascular cells and their relevance to macrovascular complications of diabetesJohn F Oram
Department of Medicine, University of Washington School of Medicine, Seattle WA 98195-7470, USA
Front Biosci 9:1240-53. 2004..Certain NEFAs liberated from triglycerides may therefore play an important role in accelerating atherosclerosis caused by diabetes by directly affecting the key cell types involved in atherogenesis... - IGF-1 induces rat glomerular mesangial cells to accumulate triglycerideAnne K Berfield
Univ of Washington School of Medicine and Department of Medicine, Veterans Affairs Puget Sound Health Care System, 1660 South Columbian Way, Seattle, WA 98108, USA
Am J Physiol Renal Physiol 290:F138-47. 2006..These observations are relevant to understanding vascular disease and progressive renal diseases that are accelerated by abnormalities in lipid metabolism... - The myeloperoxidase product hypochlorous acid oxidizes HDL in the human artery wall and impairs ABCA1-dependent cholesterol transportConstanze Bergt
Department of Medicine, University of Washington School of Medicine, Seattle, WA 98195, USA
Proc Natl Acad Sci U S A 101:13032-7. 2004.... - Oxidized HDL: the paradox-idation of lipoproteinsConstanze Bergt
Arterioscler Thromb Vasc Biol 23:1488-90. 2003 - Unsaturated fatty acids phosphorylate and destabilize ABCA1 through a protein kinase C delta pathwayYutong Wang
Department of Medicine, University of Washington, Seattle, WA 98195, USA
J Lipid Res 48:1062-8. 2007..These data indicate that unsaturated fatty acids destabilize ABCA1 by activating a PKCdelta pathway that phosphorylates ABCA1 serines... - Human atherosclerotic intima and blood of patients with established coronary artery disease contain high density lipoprotein damaged by reactive nitrogen speciesSubramaniam Pennathur
Department of Medicine, School of Medicine, University of Washington, Seattle, Washington 98195, USA
J Biol Chem 279:42977-83. 2004..Thus, nitrated HDL might represent a previously unsuspected link between nitrosative stress, atherosclerosis, and inflammation... - Shotgun proteomics implicates protease inhibition and complement activation in the antiinflammatory properties of HDLTomas Vaisar
Department of Medicine, University of Washington School of Medicine, Seattle, Washington 98195, USA
J Clin Invest 117:746-56. 2007....
Research Grants
- Modulation of ABCA1 Expression and ActivityJohn Oram; Fiscal Year: 2007..These studies will suggest possible sites of impairment of the ABCA1 pathway and uncover potential therapeutic targets for treating cardiovascular disease. ..
- Atherogenic Effects of Oxidized High Density LipoproteinsJohn Oram; Fiscal Year: 2006....
- Atherogenic Effects of Tyrosine Oxidation in HDLJohn Oram; Fiscal Year: 2004....
- CELLULAR DISORDERS IN FAMILIAL HDL DEFICIENCIESJohn Oram; Fiscal Year: 2003..These studies will help design therapeutic approaches for correcting cellular disorders associated with low plasma HDL and increased risk for heart disease. ..
- Anti-inflammatory, cholesterol export, and cardioprotective functions of ABCA1John Oram; Fiscal Year: 2009..This research will investigate the cell pathways involved in the cholesterol removal and anti-inflammatory actions of ABCA1 and determine if these pathways protect against heart disease in animals. ..