H B Brewer

Washington Hospital Center, Washington, Washington, D.C., United States

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Publications (233)1656.17 Total impact

  • Atherosclerosis Supplements 06/2006; 7(3):482-482. DOI:10.1016/S1567-5688(06)81926-4 · 9.67 Impact Factor
  • Atherosclerosis Supplements 06/2006; 7(3):320-320. DOI:10.1016/S1567-5688(06)81281-X · 9.67 Impact Factor
  • 6th Annual Conference on Arteriosclerosis, Thrombosis and Vascular; 05/2005
  • 6th Annual Conference on Arteriosclerosis, Thrombosis and Vascular; 05/2005
  • Atherosclerosis Supplements 09/2003; 4(2):137. DOI:10.1016/S1567-5688(03)90588-5 · 9.67 Impact Factor
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    S Santamarina-Fojo · A T Remaley · E B Neufeld · H. B. Jr. Brewer
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    ABSTRACT: The discovery of the role of the ATP-binding cassette transporter A1 (ABCA1) in mediating apolipoprotein A-I-mediated efflux has led to a dramatic increase in our knowledge of the molecular mechanisms involved in cholesterol efflux and cellular metabolism. In this review, we discuss several aspects of ABCA1 regulation including i) transcriptional regulation, ii) substrate specificity and availability, iii) accessory proteins, iv) acceptor specificity and availability, and v) protein trafficking. The majority of studies of ABCA1 regulation to date have focused on the identification of promoter elements that determine ABCA1 gene transcription. Here we also review the potential functional role of ABCA1 in reverse cholesterol transport. Given the key role that ABCA1 plays in cholesterol homeostasis, it is likely that there are multiple mechanisms for controlling the overall transporter activity of ABCA1.
    The Journal of Lipid Research 10/2001; 42(9):1339-45. · 4.73 Impact Factor
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    ABSTRACT: To evaluate the biochemical and molecular mechanisms leading to glomerulosclerosis and the variable development of atherosclerosis in patients with familial lecithin cholesterol acyl transferase (LCAT) deficiency, we generated LCAT knockout (KO) mice and cross-bred them with apolipoprotein (apo) E KO, low density lipoprotein receptor (LDLr) KO, and cholesteryl ester transfer protein transgenic mice. LCAT-KO mice had normochromic normocytic anemia with increased reticulocyte and target cell counts as well as decreased red blood cell osmotic fragility. A subset of LCAT-KO mice accumulated lipoprotein X and developed proteinuria and glomerulosclerosis characterized by mesangial cell proliferation, sclerosis, lipid accumulation, and deposition of electron dense material throughout the glomeruli. LCAT deficiency reduced the plasma high density lipoprotein (HDL) cholesterol (-70 to -94%) and non-HDL cholesterol (-48 to -85%) levels in control, apoE-KO, LDLr-KO, and cholesteryl ester transfer protein-Tg mice. Transcriptome and Western blot analysis demonstrated up-regulation of hepatic LDLr and apoE expression in LCAT-KO mice. Despite decreased HDL, aortic atherosclerosis was significantly reduced (-35% to -99%) in all mouse models with LCAT deficiency. Our studies indicate (i) that the plasma levels of apoB containing lipoproteins rather than HDL may determine the atherogenic risk of patients with hypoalphalipoproteinemia due to LCAT deficiency and (ii) a potential etiological role for lipoproteins X in the development of glomerulosclerosis in LCAT deficiency. The availability of LCAT-KO mice characterized by lipid, hematologic, and renal abnormalities similar to familial LCAT deficiency patients will permit future evaluation of LCAT gene transfer as a possible treatment for glomerulosclerosis in LCAT-deficient states.
    Journal of Biological Chemistry 06/2001; 276(18):15090-8. DOI:10.1074/jbc.M008466200 · 4.57 Impact Factor
  • R D Shamburek · H B Brewer · B R Gochuico
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    ABSTRACT: Erdheim-Chester disease (ECD) is a rare multisystem histiocytosis syndrome of unknown cause that usually affects adults. Histiocytic infiltration of multiple end organs produces bone pain, xanthelasma and xanthoma, exophthalmos, diabetes insipidus, and interstitial lung disease. Differential diagnosis includes Langerhans cell histiocytosis, metabolic disorders, malignancy, and sarcoidosis. ECD can be diagnosed using a combination of clinical and histopathologic findings. Sites of involvement include lung, bone, skin, retroorbital tissue, central nervous system, pituitary gland, retroperitoneum, and pericardium. Symmetrical long bone pain with associated osteosclerotic lesions, xanthomas around the eyelids, exophthalmos, and/or diabetes insipidus suggest ECD. Approximately 35% of patients have associated lung involvement, characterized by interstitial accumulations of histiocytic cells and fibrosis in a predominantly perilymphangitic and subpleural pattern. This pattern distinguishes ECD from other histiocytic disorders involving the lung. The diagnosis is confirmed by tissue biopsies that contain histiocytes with non-Langerhans cell features. In general, the clinical course of patients with this disease varies, and the prognosis can be poor despite treatment. Clinical trials for treatment of ECD have not been conducted and treatment is based on anecdotal experience.
    The American Journal of the Medical Sciences 02/2001; 321(1):66-75. · 1.52 Impact Factor
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    ABSTRACT: Peroxisome proliferator-activated receptors (PPARs) are nuclear receptors that regulate lipid and glucose metabolism and cellular differentiation. PPAR-alpha and PPAR-gamma are both expressed in human macrophages where they exert anti-inflammatory effects. The activation of PPAR-alpha may promote foam-cell formation by inducing expression of the macrophage scavenger receptor CD36. This prompted us to investigate the influence of different PPAR-activators on cholesterol metabolism and foam-cell formation of human primary and THP-1 macrophages. Here we show that PPAR-alpha and PPAR-gamma activators do not influence acetylated low density lipoprotein-induced foam-cell formation of human macrophages. In contrast, PPAR-alpha and PPAR-gamma activators induce the expression of the gene encoding ABCA1, a transporter that controls apoAI-mediated cholesterol efflux from macrophages. These effects are likely due to enhanced expression of liver-x-receptor alpha, an oxysterol-activated nuclear receptor which induces ABCA1-promoter transcription. Moreover, PPAR-alpha and PPAR-gamma activators increase apoAI-induced cholesterol efflux from normal macrophages. In contrast, PPAR-alpha or PPAR-gamma activation does not influence cholesterol efflux from macrophages isolated from patients with Tangier disease, which is due to a genetic defect in ABCA1. Here we identify a regulatory role for PPAR-alpha and PPAR-gamma in the first steps of the reverse-cholesterol-transport pathway through the activation of ABCA1-mediated cholesterol efflux in human macrophages.
    Nature Medicine 02/2001; 7(1):53-8. DOI:10.1038/83348 · 28.05 Impact Factor
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    ABSTRACT: The thoracic aorta is an important site of atherosclerotic disease in patients with homozygous familial hypercholesterolemia (HFH). Thoracic aortic atherosclerosis in patients with HFH was assessed with contrast-enhanced MR angiograms using exoscopic and endoscopic virtual angioscopy reconstructions and maximum intensity projections (MIPs). Contrast-enhanced MR angiograms of the thoracic aorta of 15 patients with HFH and 8 normal volunteers were obtained. Perspective surface reconstructions of the MR angiograms including virtual angioscopy views were evaluated by three radiologists blinded to the diagnosis. Thoracic wall irregularity was depicted on 8 of 15 (53%) patient scans and only 1 of 8 (13%) normal subject scans using surface reconstructions. Wall irregularity scores of patients with HFH were significantly increased compared with controls (2.0 +/- 0.9 vs. 1.0 +/- 0.6; p = 0.008). There was excellent interobserver agreement (weighted kappa = 0.82 +/- 0.12). Virtual endoscopy views added diagnostic confidence compared with exoscopic surface renderings alone. MIP reconstructions were unable to depict wall irregularity. MR angiography with virtual angioscopy of the thoracic aorta depicts nonstenotic wall irregularity of thoracic aortic atherosclerosis in patients with HFH. This may be important for assessing disease progression and response to treatment and may be generalizable to routine (non-HFH) atherosclerosis.
    Journal of Computer Assisted Tomography 01/2001; 25(3):371-7. DOI:10.1097/00004728-200105000-00008 · 1.60 Impact Factor
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    ABSTRACT: The ABCA1 gene, a member of the ATP-binding cassette A (ABCA1) transporter superfamily, encodes a membrane protein that facilitates the cellular efflux of cholesterol and phospholipids. Mutations in ABCA1 lead to familial high density lipoprotein deficiency and Tangier disease. We report the complete human ABCA1 gene sequence, including 1,453 bp of the promoter, 146,581 bp of introns and exons, and 1 kb of the 3' flanking region. The ABCA1 gene spans 149 kb and comprises 50 exons. Sixty-two repetitive Alu sequences were identified in introns 1-49. The transcription start site is 315 bp upstream of a newly identified initiation methionine codon and encodes an ORF of 6,783 bp. Thus, the ABCA1 protein is comprised of 2,261 aa. Analysis of the 1,453 bp 5' upstream of the transcriptional start site reveals multiple binding sites for transcription factors with roles in lipid metabolism. Comparative analysis of the mouse and human ABCA1 promoter sequences identified specific regulatory elements, which are evolutionarily conserved. The human ABCA1 promoter fragment -200 to -80 bp that contains binding motifs for SP1, SP3, E-box, and AP1 modulates cellular cholesterol and cAMP regulation of ABCA1 gene expression. These combined findings provide insights into ABCA1-mediated regulation of cellular cholesterol metabolism and will facilitate the identification of new pharmacologic agents for the treatment of atherosclerosis in humans.
    Proceedings of the National Academy of Sciences 08/2000; 97(14):7987-92. DOI:10.1073/pnas.97.14.7987 · 9.81 Impact Factor
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    ABSTRACT: Recent in vitro studies have provided evidence that hepatic lipase (HL) facilitates the selective uptake of HDL cholesteryl esters (CE), but the in vivo physiological relevance of this process has not been demonstrated. To evaluate the role that HL plays in facilitating the selective uptake of HDL-CE in vivo, we studied the metabolism of [(3)H]CEt, (125)I-labeled apolipoprotein (apo) A-I, and (131)I-labeled apoA-II-labeled HDL in HL-deficient mice. Kinetic analysis revealed similar catabolism of (125)I-labeled apoA-I (as well as (131)I-labeled apoA-II) in C57BL controls and HL deficient mice, with fractional catabolic rates (FCR) of 2.17 +/- 0.15 and 2.16 +/- 0.11 d(-)(1) (2.59 +/- 0.14 and 2.67 +/- 0.13 d(-)(1), respectively). In contrast, despite similar hepatic scavenger receptor BI expression, HL-deficient mice had delayed clearance of [(3)H]CEt compared to controls (FCR = 3.66 +/- 0.29 and 4.41 +/- 0.18 d(-)(1), P < 0.05). The hepatic accumulation of [(3)H]CEt in HL-deficient mice (62.3 +/- 2.1% of total) was significantly less than in controls (72.7 +/- 3.0%), while the [(3)H]CEt remaining in the plasma compartment increased (20.7 +/- 1.8% and 12.6 +/- 0.5%) (P < 0.05, all). In summary, HL deficiency does not alter the catabolism of apoA-I and apoA-II but decreases the hepatic uptake and the plasma clearance of HDL-CE. These data establish for the first time an important role for HL in facilitating the selective uptake of HDL-CE in vivo.
    The Journal of Lipid Research 06/2000; 41(5):667-72. · 4.73 Impact Factor
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    ABSTRACT: To investigate the in vivo role that hepatic lipase (HL) plays in HDL metabolism independently of its lipolytic function, recombinant adenovirus (rAdV) expressing native HL, catalytically inactive HL (HL-145G), and luciferase control was injected in HL-deficient mice. At day 4 after infusion of 2 x 10(8) plaque-forming units of rHL-AdV and rHL-145G-AdV, similar plasma concentrations were detected in postheparin plasma (HL=8.4+/-0.8 microg/mL and HL-145G=8.3+/-0.8 microg/mL). Mice expressing HL had significant reductions of cholesterol (-76%), phospholipids (PL; -68%), HDL cholesterol (-79%), apolipoprotein (apo) A-I (-45%), and apoA-II (-59%; P<0.05 for all), whereas mice expressing HL-145G decreased their cholesterol (-49%), PL (-40%), HDL cholesterol (-42%), and apoA-II (-89%; P<0.005 for all) but had no changes in apoA-I. The plasma kinetics of (125)I-labeled apoA-I HDL, (131)I-labeled apoA-II HDL, and [(3)H]cholesteryl ester (CE) HDL revealed that compared with mice expressing luciferase control (fractional catabolic rate [FCR] in d(-1): apoA-I HDL=1.3+/-0.1; apoA-II HDL=2.1+/-0; CE HDL=4.1+/-0.7), both HL and HL-145G enhanced the plasma clearance of CEs and apoA-II present in HDL (apoA-II HDL=5.6+/-0.5 and 4.4+/-0.2; CE HDL=9.3+/-0. 0 and 8.3+/-1.1, respectively), whereas the clearance of apoA-I HDL was enhanced in mice expressing HL (FCR=4.6+/-0.3) but not HL-145G (FCR=1.4+/-0.4). These combined findings demonstrate that both lipolytic and nonlipolytic functions of HL are important for HDL metabolism in vivo. Our study provides, for the first time, in vivo evidence for a role of HL in HDL metabolism independent of lipolysis and provides new insights into the role of HL in facilitating distinct metabolic pathways involved in the catabolism of apoA-I- versus apoA-II-containing HDL.
    Arteriosclerosis Thrombosis and Vascular Biology 03/2000; 20(3):793-800. DOI:10.1161/01.ATV.20.3.793 · 5.53 Impact Factor
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    ABSTRACT: Hepatic lipase (HL) plays a major role in high-density lipoprotein (HDL) metabolism both as a lipolytic enzyme and as a ligand. To investigate whether HL enhances the uptake of HDL-cholesteryl ester (CE) via the newly described scavenger receptor BI (SR-BI), we measured the effects of expressing HL and SR-BI on HDL-cell association as well as uptake of 125I-labeled apoA-I and [3H]CE-HDL, by embryonal kidney 293 cells. As expected, HDL cell association and CE selective uptake were increased in SR-BI transfected cells by 2- and 4-fold, respectively, compared to controls (P < 0.001). Cells transfected with HL alone or in combination with SR-BI expressed similar amounts of HL, 20% of which was bound to cell surface proteoglycans. HL alone increased HDL cell association by 2-fold but had no effect on HDL-CE uptake in 293 cells. However, in cells expressing SR-BI, HL further enhanced the selective uptake of CE from HDL by 3-fold (P < 0.001). To determine whether the lipolytic and/or ligand function of HL are required in this process, we generated a catalytically inactive form of HL (HL-145G). Cells co-transfected with HL-145G and SR-BI increased their HDL cell association and HDL-CE selective uptake by 1.4-fold compared to cells expressing SR-BI only (P < 0.03). Heparin abolished the effect of HL-145G on SR-BI-mediated HDL-CE selective uptake.Thus, the enhanced uptake of HDL-CE by HL is mediated by both its ligand role, which requires interaction with proteoglycans, and by lipolysis with subsequent HDL particle remodeling. These results establish HL as a major modulator of SR-BI mediated selective uptake of HDL-CE.
    The Journal of Lipid Research 07/1999; 40(7):1294-303. · 4.73 Impact Factor
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    ABSTRACT: We have investigated the role of hepatic lipase (HL) in remnant lipoprotein metabolism independent of lipolysis by using recombinant adenovirus to express native and catalytically inactive HL (HL-145G) in apolipoprotein (apo)E-deficient mice characterized by increased plasma concentrations of apoB-48-containing remnants. In the absence of apoE, the mechanisms by which apoB-48-containing remnants are taken up by either low density lipoprotein (LDL)-receptor or LDL-receptor-related protein (LRP) remain unclear. Overexpression of either native or catalytically inactive HL in apoE-deficient mice led to similar reductions (P > 0.5) in the plasma concentrations of cholesterol (41% and 53%) and non high density lipoprotein (HDL)-cholesterol (41% and 56%) indicating that even in the absence of lipolysis, HL can partially compensate for the absence of apoE in this animal model. Although the clearance of [3H]cholesteryl ether from VLDL was significantly increased (approximately 2-fold; P < 0. 02) in mice expressing native or inactive HL compared to luciferase controls, the fractional catabolic rates (FCR) of [125I-labeled] apoB- very low density lipoprotein (VLDL) in all three groups of mice were similar (P > 0.4, all) indicating selective cholesterol uptake. Hepatic uptake of [3H]cholesteryl ether from VLDL was greater in mice expressing either native HL (87%) or inactive HL-145G (72%) compared to luciferase controls (56%). Our combined findings are consistent with a role for HL in mediating the selective uptake of cholesterol from remnant lipoproteins in apoE-deficient mice, independent of lipolysis. These studies support the concept that hepatic lipase (HL) may serve as a ligand that mediates the interaction between remnant lipoproteins and cell surface receptors and/or proteoglycans. We hypothesize that one of these pathways may involve the interaction of HL with cell surface receptors, such as scavenger receptor (SR)-BI, that mediate the selective uptake of cholesteryl esters.
    The Journal of Lipid Research 01/1999; 39(12):2436-42. · 4.73 Impact Factor
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    ABSTRACT: Supplemental vitamin E does not raise plasma alpha-tocopherol concentrations more than approximately 3-fold. To elucidate the mechanism for the limitation in plasma alpha-tocopherol, we undertook human supplementation trials using incrementally increased doses of deuterated vitamin E. Plasma was obtained from 6 healthy, young adults (4 men and 2 women) during 3 sequential supplementation trials with doses of 15, 75, and 150 mg RRR-alpha-tocopheryl acetate labeled with deuterium (d3-RRR-alpha-tocopheryl acetate). A defined diet was provided on the day of deuterated vitamin E administration, but otherwise subjects ate ad libitum. The areas under the curves calculated from the plasma d3-RRR-alpha-tocopherol concentrations increased linearly with dose--a 10-fold increase in dose resulted in a 10-fold increase in area under the curve. d3-RRR-alpha-Tocopherol absorption and incorporation into plasma did not decrease with increasing dose. At 11 h, the 15-, 75-, and 150-mg doses resulted in 8+/-4%, 21+/-10%, and 37+/-20% labeling, respectively, of plasma vitamin E. Plasma total (labeled plus unlabeled) alpha-tocopherol concentrations before supplementation were 12+/-3 micromol/L and over the 96 h after the dose averaged 13.3+/-2.6, 15.4+/-3.0, and 16.7+/-4.9 micromol/L for the 15-, 75-, and 150-mg doses, respectively. d3-RRR-alpha-Tocopherol was incorporated into the plasma in preference to circulating plasma RRR-alpha-tocopherol. This could occur if the newly absorbed d3-RRR-alpha-tocopherol was preferentially used to replenish circulating vitamin E.
    American Journal of Clinical Nutrition 11/1998; 68(4):847-53. · 6.92 Impact Factor
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    E Lesma · J Moss · H B Brewer · R Bortell · D Greiner · J Mordes · A A Rossini
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    ABSTRACT: RT6 is a rat lymphocyte glycosylphosphatidylinositol (GPI)-anchored alloantigen with nicotinamide adenine dinucleotide (NAD) glycohydrolase (NADase) and auto-ADP-ribosyltransferase activities. RT6 may have immunoregulatory properties based in part on the observation that injection of diabetes-resistant (DR)-BB rats with depleting doses of anti-RT6.1 mAb induced autoimmune diabetes and thyroiditis. We now report that injection of DR-BB rats with anti-RT6.1 mAb increased plasma NADase activity, which localized, by fluid phase liquid chromatography fractionation, to the high density lipoprotein (HDL) fraction. Following ultracentrifugation in high salt, however, RT6 was found in the nonlipoprotein fraction, where it existed, under nondenaturing conditions, as a 200-kDa complex and, by SDS-PAGE, as a 30- to 36-kDa species. Thy-1, another GPI-linked protein, and proteins that reacted with anti-GPI-oligosaccharide Abs also translocated from HDL to the nonlipoprotein fraction under similar conditions. Injection of anti-RT6.1 mAb into thymectomized DR and diabetes-prone-BB rats increased soluble RT6 to levels comparable to those observed in euthymic DR-BB rats, suggesting that HDL-bound RT6 is not derived from peripheral lymphocytes. In agreement, NADase activity in the plasma of eviscerated DR-BB rats did not increase following injection of anti-RT6 mAb. These data suggest that HDL is a carrier of plasma RT6 and other GPI-linked proteins, with equilibrium between the lipoprotein and nonlipoprotein fractions being salt dependent. Since GPI-linked proteins in HDL can transfer to cells in a functionally active form, the presence of RT6 in HDL is consistent with it having a role in signaling in nonlymphoid cells.
    The Journal of Immunology 09/1998; 161(3):1212-9. · 5.36 Impact Factor
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    ABSTRACT: Familial hypercholesterolemia (FH), a disease caused by a variety of mutations in the low density lipoprotein receptor (LDLr) gene, leads not only to elevated LDL-cholesterol (C) concentrations but to reduced high density lipoprotein (HDL)-C and apolipoprotein (apo) A-I concentrations as well. The reductions in HDL-C and apoA-I are the consequence of the combined metabolic defects of increased apoA-I catabolism and decreased apoA-I synthesis. The present studies were designed to test the hypothesis that overexpression of human lecithin:cholesterol acyltransferase (hLCAT), a pivotal enzyme involved in HDL metabolism, in LDLr defective rabbits would increase HDL-C and apoA-I concentrations. Two groups of hLCAT transgenic rabbits were established: 1) hLCAT+/LDLr heterozygotes (LDLr+/-) and 2) hLCAT+/LDLr homozygotes (LDLr-/-). Data for hLCAT+ rabbits were compared to those of nontransgenic (hLCAT-) rabbits of the same LDLr status. In LDLr+/- rabbits, HDL-C and apoA-I concentrations (mg/dl), respectively, were significantly greater in hLCAT+ (62 +/- 8, 59 +/- 4) relative to hLCAT- rabbits (21 +/- 1, 26 +/- 2). This was, likewise, the case when hLCAT+/ LDLr-/- (27 +/- 2, 19 +/- 6) and hLCAT-/LDLr-/- (5 +/- 1, 6 +/- 2) rabbits were compared. Kinetic experiments demonstrated that the fractional catabolic rate (FCR, d(-1)) of apoA-I was substantially delayed in hLCAT+ (0.376 +/- 0.025) versus hLCAT- (0.588) LDLr+/- rabbits, as well as in hLCAT+ (0.666 +/- 0.033) versus hLCAT- (1.194 +/- 0.138) LDLr-/- rabbits. ApoA-I production rate (PR, mg x kg x d(-1)) was greater in both hLCAT+/LDLr+/- (10 +/- 2 vs. 6) and hLCAT+/LDLr-/- (9 +/- 1 vs. 4 +/- 1) rabbits. Significant correlations (P < 0.02) were observed between plasma LCAT activity and HDL-C (r = 0.857), apoA-I FCR (r = -0.774), and apoA-I PR (r = 0.771), while HDL-C correlated with both apoA-I FCR (-0.812) and PR (0.751). In summary, these data indicate that hLCAT overexpression in LDLr defective rabbits increases HDL-C and apoA-I concentrations by both decreasing apoA-I catabolism and increasing apoA-I synthesis, thus correcting the metabolic defects responsible for the hypoalphalipoproteinemia observed in LDLr deficiency.
    The Journal of Lipid Research 08/1998; 39(8):1558-67. · 4.73 Impact Factor
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    A T Remaley · B D Farsi · A C Shirali · J M Hoeg · H B Brewer
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    ABSTRACT: Epithelial cells contain two distinct membrane surfaces, the apical and basolateral plasma membranes, which have different lipid and protein compositions. In order to assess the effect of the compositional differences of the apical and basolateral membranes on their ability to undergo cholesterol efflux, MDCK cells were radiolabeled with [3H]cholesterol and grown as a polarized monolayer on filter inserts, that separate the upper apical compartment from the lower basolateral compartment. The rate of cholesterol efflux from the basolateral membrane into media containing HDL in the basolateral compartment was 6.3%/h +/-0.7, whereas HDL-mediated efflux from the apical membrane was approximately 3-fold slower (1.9%/h +/-0.3). In contrast, Fu5AH cells, which do not form distinct polarized membrane domains, had a similar rate of HDL-mediated cholesterol efflux into the apical and basolateral compartments. Similar to HDL, other cholesterol acceptors, namely LDL, bovine serum albumin, and a lipid emulsion, also showed a decreased rate of cholesterol efflux from the apical membrane surface versus the basolateral membrane. Compared to the basolateral membrane, the apical membrane was also found to be more resistant to cholesterol oxidase treatment, to bind less HDL, and to take up less cholesterol from the medium. In conclusion, cholesterol efflux occurred less readily from the apical membrane than from the basolateral membrane for all types of acceptors tested. These results suggest that differences in the composition of the apical and basolateral membrane lead to a relative decrease in cholesterol desorption from the apical membrane and hence a reduced rate of cholesterol efflux.
    The Journal of Lipid Research 07/1998; 39(6):1231-8. · 4.73 Impact Factor
  • J C Fruchart · H. B. Jr. Brewer · E Leitersdorf
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    ABSTRACT: The hypolipidemic action of fibrates has recently been shown to involve the activation of peroxisome proliferator activated receptors establishing a molecular mechanism for this class of drugs. Increasing clinical trial evidence supports the efficacy of fibrates in the treatment of dyslipoproteinemias, particularly in patients with hypertriglyceridemia and low high-density lipoproteins.
    The American Journal of Cardiology 05/1998; 81(7):912-7. DOI:10.1016/S0002-9149(98)00010-1 · 3.43 Impact Factor

Publication Stats

9k Citations
1,656.17 Total Impact Points


  • 2006
    • Washington Hospital Center
      Washington, Washington, D.C., United States
  • 1973–2001
    • National Heart, Lung, and Blood Institute
      • Hematology Branch
      Maryland, United States
  • 2000
    • Institut Pasteur de Lille
      Lille, Nord-Pas-de-Calais, France
  • 1999
    • Cornell University
      • Department of Nutritional Sciences
      Ithaca, New York, United States
  • 1998
    • Oregon State University
      Corvallis, Oregon, United States
  • 1968–1998
    • National Institutes of Health
      • • Center for Clinical Research
      • • Molecular Targets Laboratory
      Maryland, United States
  • 1997
    • University of Chicago
      Chicago, Illinois, United States
  • 1994
    • Yamagata University
      Ямагата, Yamagata, Japan
  • 1991
    • Northern Inyo Hospital
      BIH, California, United States
  • 1984
    • Roswell Park Cancer Institute
      • Department of Human Genetics
      Buffalo, New York, United States
  • 1983
    • Walter Reed National Military Medical Center
      Washington, Washington, D.C., United States
  • 1977
    • University of North Carolina at Chapel Hill
      • Department of Medicine
      Chapel Hill, NC, United States