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Journal of Receptor, Ligand and Channel Research Volume 3, 2010 - Issue
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Review

Overview of the LDL receptor: relevance to cholesterol metabolism and future approaches for the treatment of coronary heart disease

William R LagorDepartment of Pharmacology, Institute for Translational Research and Therapeutics, University of Pennsylvania, Philadelphia, PA, USA
&
John S MillarDepartment of Pharmacology, Institute for Translational Research and Therapeutics, University of Pennsylvania, Philadelphia, PA, USACorrespondence[email protected]
Pages 1-14 | Published online: 17 Dec 2009

References

  • Warner GJ, Stoudt G, Bamberger M, Johnson WJ, Rothblat GH. Cell toxicity induced by inhibition of acyl coenzyme A:cholesterol acyl-transferase and accumulation of unesterified cholesterol. J Biol Chem. 1995;270(11):5772–5778.
  • Brown MS, Goldstein JL. Sterol regulatory element binding proteins (SREBPs): controllers of lipid synthesis and cellular uptake. Nutr Rev. 1998;56(2 Pt 2):S1–S3; discussion S54-S75.
  • Slater HR, McKinney L, Packard CJ, Shepherd J. Contribution of the receptor pathway to low density lipoprotein catabolism in humans. New methods for quantitation. Arteriosclerosis. 1984;4(6):604–613.
  • Brown MS, Goldstein JL. Cholesterol feedback: from Schoenheimer’s bottle to Scap’s MELADL. J Lipid Res. 2009;50(Suppl):S15–S27.
  • Goldstein JL, Brown MS. The LDL receptor. Arterioscler Thromb Vasc Biol. 2009;29(4):431–438.
  • Hobbs HH, Brown MS, Goldstein JL. Molecular genetics of the LDL receptor gene in familial hypercholesterolemia. Hum Mutat. 1992;1(6):445–466.
  • Muller C. Angina pectoris in heriditary xanthomatosis. Arch Intern Med. 1939;64:675–700.
  • Goldstein JL, Brown MS. Familial hypercholesterolemia: identification of a defect in the regulation of 3-hydroxy-3-methylglutaryl coenzyme A reductase activity associated with overproduction of cholesterol. Proc Natl Acad Sci U S A. 1973;70(10):2804–2808.
  • Brown MS, Goldstein JL. Familial hypercholesterolemia: defective binding of lipoproteins to cultured fibroblasts associated with impaired regulation of 3-hydroxy-3-methylglutaryl coenzyme A reductase activity. Proc Natl Acad Sci U S A. 1974;71(3):788–792.
  • Brown MS, Goldstein JL. Regulation of the activity of the low density lipoprotein receptor in human fibroblasts. Cell. 1975;6(3):307–316.
  • Schneider WJ, Beisiegel U, Goldstein JL, Brown MS. Purification of the low density lipoprotein receptor, an acidic glycoprotein of 164,000 molecular weight. J Biol Chem. 1982;257(5):2664–2673.
  • Sudhof TC, Goldstein JL, Brown MS, Russell DW. The LDL receptor gene: a mosaic of exons shared with different proteins. Science. 1985;228(4701):815–822.
  • Brown MS, Herz J, Goldstein JL. LDL-receptor structure. Calcium cages, acid baths and recycling receptors. Nature. 1997;388(6643):629–630.
  • Kolansky DM, Cuchel M, Clark BJ, et al. Longitudinal evaluation and assessment of cardiovascular disease in patients with homozygous familial hypercholesterolemia. Am J Cardiol. 2008;102(11):1438–1443.
  • Shireman R, Kilgore LL, Fisher WR. Solubilization of apolipoprotein B and its specific binding by the cellular receptor for low density lipoprotein. Proc Natl Acad Sci U S A. 1977;74(11):5150–5154.
  • Mahley RW, Innerarity TL, Weisgraber KH, Fry DL. Canine hyperlipoproteinemia and atherosclerosis. Accumulation of lipid by aortic medial cells in vivo and in vitro. Am J Pathol. 1977;87(1):205–226.
  • Yamamoto T, Davis CG, Brown MS, et al. The human LDL receptor: a cysteine-rich protein with multiple Alu sequences in its mRNA. Cell. 1984;39(1):27–38.
  • Mahley RW, Weisgraber KH, Melchior GW, Innerarity TL, Holcombe KS. Inhibition of receptor-mediated clearance of lysine and arginine-modified lipoproteins from the plasma of rats and monkeys. Proc Natl Acad Sci US A. 1980;77(1):225–229.
  • Innerarity TL, Friedlander EJ, Rail SC Jr, Weisgraber KH, Mahley RW. The receptor-binding domain of human apolipoprotein E. Binding of apolipoprotein E fragments. J Biol Chem. 1983;258(20):12341–12347.
  • Kita T, Brown MS, Watanabe Y, Goldstein JL. Deficiency of low density lipoprotein receptors in liver and adrenal gland of the WHHL rabbit, an animal model of familial hypercholesterolemia. Proc Natl Acad Sci U S A. 1981;78(4):2268–2272.
  • Russell DW, Schneider WJ, Yamamoto T, et al. Domain map of the LDL receptor: sequence homology with the epidermal growth factor precursor. Cell. 1984;37(2):577–585.
  • Jeon H, Meng W, Takagi J, Eck MJ, Springer TA, Blacklow SC. Implications for familial hypercholesterolemia from the structure of the LDL receptor YWTD-EGF domain pair. Nat Struct Biol. 2001;8(6):499–504.
  • Rudenko G, Henry L, Henderson K, et al. Structure of the LDL receptor extracellular domain at endosomal pH. Science. 2002;298(5602):2353–2358.
  • Kozarsky K, Kingsley D, Krieger M. Use of a mutant cell line to study the kinetics and function of O-linked glycosylation of low density lipoprotein receptors. Proc Natl Acad Sci U S A. 1988;85(12):4335–4339.
  • Davis CG, Elhammer A, Russell DW, et al. Deletion of clustered
  • O-linked carbohydrates does not impair function of low density lipoprotein receptor in transfected fibroblasts. J Biol Chem. 1986;261(6):2828–2838.
  • Lehrman MA, Schneider WJ, Sudhof TC, et al. Mutation in LDL receptor: Alu-Alu recombination deletes exons encoding transmembrane and cytoplasmic domains. Science. 1985;227(4683):140–146.
  • Garcia CK, Wilund K, Arca M, et al. Autosomal recessive hypercholesterolemia caused by mutations in a putative LDL receptor adaptor protein. Science. 2001;292(5520):1394–1398.
  • Koivisto UM, Hubbard AL, Mellman I. A novel cellular phenotype for familial hypercholesterolemia due to a defect in polarized targeting of LDL receptor. Cell. 2001;105(5):575–585.
  • Chatterton JE, Phillips ML, Curtiss LK, et al. Immunoelectron microscopy of low density lipoproteins yields a ribbon and bow model for the conformation of apolipoprotein B on the lipoprotein surface. J Lipid Res. 1995;36(9):2027–2037.
  • Packard CJ, Munro A, Lorimer AR, Gotto AM, Shepherd J. Metabolism of apolipoprotein B in large triglyceride-rich very low density lipoproteins of normal and hypertriglyceridemic subjects. J Clin Invest. 1984;74(6):2178–2192.
  • Barter PJ, Brewer HB Jr, Chapman MJ, Hennekens CH, Rader DJ, Tall AR. Cholesteryl ester transfer protein: a novel target for raising HDL and inhibiting atherosclerosis. Arterioscler Thromb Vasc Biol. 2003;23(2):160–167.
  • Krul ES, Tikkanen MJ, Cole TG, Davie JM, Schonfeld G. Roles of apolipoproteins B and E in the cellular binding of very low density lipoproteins. J Clin Invest. 1985;75(2):361–369.
  • Zaiou M, Arnold KS, Newhouse YM, et al. Apolipoprotein E;-low density lipoprotein receptor interaction. Influences of basic residue and amphipathic alpha-helix organization in the ligand. J Lipid Res. 2000;41(7):1087–1095.
  • Vega GL, Grundy SM. In vivo evidence for reduced binding of low density lipoproteins to receptors as a cause of primary moderate hypercholesterolemia. J Clin Invest. 1986;78(5):1410–1414.
  • Lamon-Fava S, Diffenderfer MR, Barrett PH, et al. Effects of different doses of atorvastatin on human apolipoprotein B-100, B-48, and A-I metabolism. J Lipid Res. 2007;48(8):1746–1753.
  • Radhakrishnan A, Goldstein JL, McDonald JG, Brown MS. Switchlike control of SREBP-2 transport triggered by small changes in ER cholesterol: a delicate balance. Cell Metab. 2008;8(6):512–521.
  • Brown MS, Goldstein JL. The SREBP pathway: regulation of cholesterol metabolism by proteolysis of a membrane-bound transcription factor. Cell. 1997;89(3):331–340.
  • Sato R, Yang J, Wang X, et al. Assignment of the membrane attachment, DNA binding, and transcriptional activation domains of sterol regulatory element-binding protein-1 (SREBP-1). J Biol Chem. 1994;269(25):17267–17273.
  • Yokoyama C, Wang X, Briggs MR, and colleagues SREBP-1, a basic-helix-loop-helix-leucine zipper protein that controls transcription of the low density lipoprotein receptor gene. Cell. 1993;75(1):187–197.
  • Hua X, Yokoyama C, Wu J, et al. SREBP-2, a second basic-helix-loop-helix-leucine zipper protein that stimulates transcription by binding to a sterol regulatory element. Proc Natl Acad Sci U S A. 1993;90(24):11603–11607.
  • Horton JD, Shah NA, Warrington JA, et al. Combined analysis of oligonucleotide microarray data from transgenic and knockout mice identifies direct SREBP target genes. Proc Natl Acad Sci U S A. 2003;100(21):12027–12032.
  • Shimano H. Sterol regulatory element-binding proteins (SREBPs): transcriptional regulators of lipid synthetic genes. Prog Lipid Res. 2001;40(6):439–452.
  • Shimano H, Shimomura I, Hammer RE, et al. Elevated levels of SREBP-2 and cholesterol synthesis in livers of mice homozygous for a targeted disruption of the SREBP-1 gene. J Clin Invest. 1997;100(8):2115–2124.
  • Natesampillai S, Fernandez-Zapico ME, Urrutia R, Veldhuis JD. A novel functional interaction between the Sp1-like protein KLF13 and SREBP-Sp1 activation complex underlies regulation of low density lipoprotein receptor promoter function. J Biol Chem. 2006;281(6):3040–3047.
  • Cohen JC, Kimmel M, Polanski A, Hobbs HH. Molecular mechanisms of autosomal recessive hypercholesterolemia. Curr Opin Lipidol. 2003;14(2):121–127.
  • Wilund KR, Yi M, Campagna F, et al. Molecular mechanisms of autosomal recessive hypercholesterolemia. Hum Mol Genet. 2002;11(24):3019–3030.
  • Khachadurian AK, Uthman SM. Experiences with the homozygous cases of familial hypercholesterolemia. A report of 52 patients. Nutr Metab. 1973;15(1):132–140.
  • Arca M, Zuliani G, Wilund K, et al. Autosomal recessive hypercholesterolaemia in Sardinia, Italy, and mutations in ARH: a clinical and molecular genetic analysis. Lancet. 2002;359(9309):841–847.
  • Zuliani G, Arca M, Signore A, et al. Characterization of a new form of inherited hypercholesterolemia: familial recessive hypercholesterolemia. Arterioscler Thromb Vasc Biol. 1999;19(3):802–809.
  • Harada-Shiba M, Tajima S, Yokoyama S, et al. Siblings with normal LDL receptor activity and severe hypercholesterolemia. Arterioscler Thromb. 1992;12(9):1071–1078.
  • He G, Gupta S, Yi M, Michaely P, Hobbs HH, Cohen JC. ARH is a modular adaptor protein that interacts with the LDL receptor, clathrin, and AP-2. J Biol Chem. 2002;277(46):44044–44049.
  • Jones C, Hammer RE, Li WP, Cohen JC, Hobbs HH, Herz J. Normal sorting but defective endocytosis of the low density lipoprotein receptor in mice with autosomal recessive hypercholesterolemia. J Biol Chem. 2003;278(31):29024–29030.
  • Garuti R, Jones C, Li WP, et al. The modular adaptor protein autosomal recessive hypercholesterolemia (ARH) promotes low density lipoprotein receptor clustering into clathrin-coated pits. J Biol Chem. 2005;280(49):40996–41004.
  • Maurer ME, Cooper JA. The adaptor protein Dab2 sorts LDL receptors into coated pits independently of AP-2 and ARH. J Cell Sci. 2006;119(Pt 20):4235–4246.
  • Zelcer N, Hong C, B oyadj ian R, T ontonoz P. LXR regulate s chole ste rol uptake through Idol-dependent ubiquitination of the LDL receptor. Science. 2009;325(5936):100–104.
  • Olsson PA, Korhonen L, Mercer EA, Lindholm D. MIR is a novel ERM-like protein that interacts with myosin regulatory light chain and inhibits neurite outgrowth. J Biol Chem. 1999;274(51):36288–36292.
  • Chait A, Bierman EL, Albers JJ. Regulatory role of triiodothyronine in the degradation of low density lipoprotein by cultured human skin fibroblasts. J Clin Endocrinol Metab. 1979;48(5):887–889.
  • Bhattacharya S, Balasubramaniam S, Simons LA. Regulation of low-density-lipoprotein metabolism in the rat. Biochem J. 1986;234(2):493–496.
  • Thompson GR, Soutar AK, Spengel FA, et al. Defects of receptor-mediated low density lipoprotein catabolism in homozygous familial hypercholesterolemia and hypothyroidism in vivo. Proc Natl Acad Sci U S A. 1981;78(4):2591–2595.
  • Staels B, Van Tol A, Chan L, Will H, Verhoeven G, Auwerx J. Alterations in thyroid status modulate apolipoprotein, hepatic triglyceride lipase, and low density lipoprotein receptor in rats. Endocrinology. 1990;127(3):1144–1152.
  • Ness GC, Pendleton LC, Li YC, Chiang JY. Effect of thyroid hormone on hepatic cholesterol 7 alpha hydroxylase, LDL receptor, HMG-CoA reductase, farnesyl pyrophosphate synthetase and apolipoprotein A-I mRNA levels in hypophysectomized rats. Biochem Biophys Res Commun. 1990;172(3):1150–1156.
  • Ness GC, Lopez D, Chambers CM, et al. Effects of L-triiodothyronine and the thyromimetic L-94901 on serum lipoprotein levels and hepatic low-density lipoprotein receptor, 3-hydroxy-3-methylglutaryl coenzyme A reductase, and apo A-I gene expression. Biochem Pharmacol. 1998;56(1):121–129.
  • Ness GC, Zhao Z. Thyroid hormone rapidly induces hepatic LDL receptor mRNA levels in hypophysectomized rats. Arch Biochem Biophys. 1994;315(1):199–202.
  • Ness GC, Lopez D. Transcriptional regulation of rat hepatic low-density lipoprotein receptor and cholesterol 7 alpha hydroxylase by thyroid hormone. Arch Biochem Biophys. 1995;323(2):404–408.
  • Bakker O, Hudig F, Meijssen S, Wiersinga WM. Effects of triiodothyronine and amiodarone on the promoter of the human LDL receptor gene. Biochem Biophys Res Commun. 1998;249(2):517–521.
  • Shin DJ, Osborne TF. Thyroid hormone regulation and cholesterol metabolism are connected through Sterol Regulatory Element-Binding Protein-2 (SREBP-2). J Biol Chem. 2003;278(36):34114–34118.
  • Lopez D, Abisambra Socarras JF, Bedi M, Ness GC. Activation of the hepatic LDL receptor promoter by thyroid hormone. Biochim Biophys Acta. 2007;1771(9):1216–1225.
  • Marcel YL, Hogue M, Weech PK, Davignon J, Milne RW. Expression of apolipoprotein B epitopes in lipoproteins. Relationship to conformation and function. Arteriosclerosis. 1988;8(6):832–844.
  • Franceschini G, Bernini F, Michelagnoli S, et al. Lipoprotein changes and increased affinity of LDL for their receptors after acipimox treatment in hypertriglyceridemia. Atherosclerosis. 1990;81(1):41–49.
  • Boren J, Lee I, Zhu W, et al. Identification of the low density lipoprotein receptor-binding site in apolipoprotein B100 and the modulation of its binding activity by the carboxyl terminus in familial defective apo-B100. J Clin Invest. 1998;101(5):1084–1093.
  • Soria LF, Ludwig EH, Clarke HR, et al. Association between a specific apolipoprotein B mutation and familial defective apolipoprotein B-100. Proc Natl Acad Sci U S A. 1989;86(2):587–591.
  • Clavey V, Lestavel-Delattre S, Copin C, Bard JM, Fruchart JC. Modulation of lipoprotein B binding to the LDL receptor by exogenous lipids and apolipoproteins CI, CII, CIII, and E. Arterioscler Thromb Vasc Biol. 1995;15(7):963–971.
  • Bradley WA, Hwang SL, Karlin JB, et al. Low-density lipoprotein receptor binding determinants switch from apolipoprotein E to apolipoprotein B during conversion of hypertriglyceridemic very-low-density lipoprotein to low-density lipoproteins. J Biol Chem. 1984;259(23):14728–14735.
  • Millar JS, Maugeais C, Fuki IV, Rader DJ. Normal production rate of apolipoprotein B in LDL receptor-deficient mice. Arterioscler Thromb Vasc Biol. 2002;22(6):989–994.
  • Millar JS, Maugeais C, Ikewaki K, et al. Complete deficiency of the low-density lipoprotein receptor is associated with increased apolipoprotein B-100 production. Arterioscler Thromb Vasc Biol. 2005;25(3):560–565.
  • Twisk J, Gillian-Daniel DL, Tebon A, et al. The role of the LDL receptor in apolipoprotein B secretion. J Clin Invest. 2000;105(4):521–532.
  • Gillian-Daniel DL, Bates PW, Tebon A, Attie AD. Endoplasmic reticulum localization of the low density lipoprotein receptor mediates presecretory degradation of apolipoprotein B. Proc Natl Acad Sci U S A. 2002;99(7):4337–4342.
  • Zheng C, Khoo C, Ikewaki K, Sacks FM. Rapid turnover of apolipoprotein C-III-containing triglyceride-rich lipoproteins contributing to the formation of LDL subfractions. J Lipid Res. 2007;48(5):1190–1203.
  • Gangabadage CS, Zdunek J, Tessari M, et al. Structure and dynamics of human apolipoprotein CIII. J Biol Chem. 2008;283(25):17416–17427.
  • Pollin TI, Damcott CM, Shen H, et al. A null mutation in human APOC3 confers a favorable plasma lipid profile and apparent cardioprotection. Science. 2008;322(5908):1702–1705.
  • Abifadel M, Varret M, Rabes JP, et al. Mutations in PCSK9 cause autosomal dominant hypercholesterolemia. Nat Genet. 2003;34(2):154–156.
  • Cohen J, Pertsemlidis A, Kotowski IK, et al. Low LDL cholesterol in individuals of African descent resulting from frequent nonsense mutations in PCSK9. Nat Genet. 2005;37(2):161–165.
  • Seidah NG, Benjannet S, Wickham L, et al. The secretory proprotein convertase neural apoptosis-regulated convertase 1 (NARC-1): liver regeneration and neuronal differentiation. Proc Natl Acad Sci U S A. 2003;100(3):928–933.
  • Zhang DW, Lagace TA, Garuti R, et al. Binding of proprotein convertase subtilisin/kexin type 9 to epidermal growth factor-like repeat A of low density lipoprotein receptor decreases receptor recycling and increases degradation. J Biol Chem. 2007;282(25):18602–18612.
  • Lagace TA, Curtis DE, Garuti R, et al. Secreted PCSK9 decreases the number of LDL receptors in hepatocytes and in livers of parabiotic mice. J Clin Invest. 2006;116(11):2995–3005.
  • Grefhorst A, McNutt MC, Lagace TA, Horton JD. Plasma PCSK9 preferentially reduces liver LDL receptors in mice. J Lipid Res. 2008;49(6):1303–1311.
  • Horton JD, Cohen JC, Hobbs HH. Molecular biology of PCSK9: its role in LDL metabolism. Trends Biochem Sci. 2007;32(2):71–77.
  • Li J, Tumanut C, Gavigan JA, et al. Secreted PCSK9 promotes LDL receptor degradation independently of proteolytic activity. Biochem J. 2007;406(2):203–207.
  • Jeong HJ, Lee HS, Kim KS, et al. Sterol-dependent regulation of proprotein convertase subtilisin/kexin type 9 expression by sterol-regulatory element binding protein-2. J Lipid Res. 2008;49(2):399–409.
  • Maxwell KN, Soccio RE, Duncan EM, Sehayek E, Breslow JL. Novel putative SREBP and LXR target genes identified by microarray analysis in liver of cholesterol-fed mice. J Lipid Res. 2003;44(11):2109–2119.
  • Dubuc G, Chamberland A, Wassef H, et al. Statins upregulate PCSK9, the gene encoding the proprotein convertase neural apoptosis-regulated convertase-1 implicated in familial hypercholesterolemia. Arterioscler Thromb Vasc Biol. 2004;24(8):1454–1459.
  • Rashid S, Curtis DE, Garuti R, et al. Decreased plasma cholesterol and hypersensitivity to statins in mice lacking Pcsk9. Proc Natl Acad Sci U S A. 2005;102(15):5374–5379.
  • Endo A, Kuroda M, Tanzawa K. Competitive inhibition of 3-hydroxy-3-methylglutaryl coenzyme A reductase by ML-236A and ML-236B fungal metabolites, having hypocholesterolemic activity. FEBS Lett. 1976;72(2):323–326.
  • Mabuchi H, Haba T, T atami R, et al. Effect of an inhibitor of 3 -hydroxy-3-methyglutaryl coenzyme A reductase on serum lipoproteins and ubiquinone-10-levels in patients with familial hypercholesterolemia. N Engl J Med. 1981;305(9):478–482.
  • Bilheimer DW, Grundy SM, Brown MS, Goldstein JL. Mevinolin and colestipol stimulate receptor-mediated clearance of low density lipoprotein from plasma in familial hypercholesterolemia heterozygotes. Proc Natl Acad Sci U S A. 1983;80(13):4124–4128.
  • Bilheimer DW, Grundy SM, Brown MS, Goldstein JL. Mevinolin stimulates receptor-mediated clearance of low density lipoprotein from plasma in familial hypercholesterolemia heterozygotes. Trans Assoc Am Physicians. 1983;96:1–9.
  • Magot T, Malmendier CL, Ouguerram K, Lontie JF, Lutton C. In vivo effect of simvastatin on lipoprotein cholesteryl ester metabolism in nor-mocholesterolemic volunteers. Clin Chim Acta. 1991;196(1):59–68.
  • Berglund L, Witztum JL, Galeano NF, et al. Three-fold effect of lovastatin treatment on low density lipoprotein metabolism in subjects with hyperlipidemia: increase in receptor activity, decrease in apoB production, and decrease in particle affinity for the receptor. Results from a novel triple-tracer approach. J Lipid Res. 1998;39(4):913–924.
  • Marais AD, Naoumova RP, Firth JC, et al. Decreased production of low density lipoprotein by atorvastatin after apheresis in homozygous familial hypercholesterolemia. J Lipid Res. 1997;38(10):2071–2078.
  • Ness GC, Zhao Z, Lopez D. Inhibitors of cholesterol biosynthesis increase hepatic low-density lipoprotein receptor protein degradation. Arch Biochem Biophys. 1996;325(2):242–248.
  • Brown MS, Anderson RG, Goldstein JL. Recycling receptors: the round-trip itinerary of migrant membrane proteins. Cell. 1983;32(3):663–667.
  • Altmann SW, Davis HR, Jr., Zhu LJ, et al. Niemann-Pick C1 Like 1 protein is critical for intestinal cholesterol absorption. Science. 2004;303(5661):1201–1204.
  • Sudhop T, Lutjohann D, Kodal A, et al. Inhibition of intestinal cholesterol absorption by ezetimibe in humans. Circulation. 2002;106(15):1943–1948.
  • Kastelein JJ, Akdim F, Stroes ES, et al. Simvastatin with or without ezetimibe in familial hypercholesterolemia. N Engl J Med. 2008;358(14):1431–1443.
  • Balmer J, Zilversmit DB. Effects of dietary roughage on cholesterol absorption, cholesterol turnover and steroid excretion in the rat. J Nutr. 1974;104(10):1319–1328.
  • Schoonjans K, Staels B, Auwerx J. Role of the peroxisome proliferator-activated receptor (PPAR) in mediating the effects of fibrates and fatty acids on gene expression. J Lipid Res. 1996;37(5):907–925.
  • Nissen SE, Nicholls SJ, Wolski K, et al. Effects of a potent and selective PPAR-alpha agonist in patients with atherogenic dyslipidemia or hypercholesterolemia: two randomized controlled trials. JAMA. 2007;297(12):1362–1373.
  • Krishna R, Anderson MS, Bergman AJ, et al. Effect of the cholesteryl ester transfer protein inhibitor, anacetrapib, on lipoproteins in patients with dyslipidaemia and on 24-h ambulatory blood pressure in healthy individuals: two double-blind, randomised placebo-controlled phase I studies. Lancet. 2007;370(9603):1907–1914.
  • Schwartz CC, Halloran LG, Vlahcevic ZR, Gregory DH, Swell L. Preferential utilization of free cholesterol from high-density lipoproteins for biliary cholesterol secretion in man. Science. 1978;200(4337):62–64.
  • Millar JS, Brousseau ME, Diffenderfer MR, et al. Effects of the cholesteryl ester transfer protein inhibitor torcetrapib on apolipoprotein B100 metabolism in humans. Arterioscler Thromb Vasc Biol. 2006;26(6):1350–1356.
  • Packard CJ, Shepherd J, Lindsay GM, Gaw A, Taskinen MR. Thyroid replacement therapy and its influence on postheparin plasma lipases and apolipoprotein-B metabolism in hypothyroidism. J Clin Endocrinol Metab. 1993;76(5):1209–1216.
  • Grover GJ, Mellstrom K, Malm J. Development of the thyroid hormone receptor beta-subtype agonist KB-141: a strategy for body weight reduction and lipid lowering with minimal cardiac side effects. Cardiovasc Drug Rev. 2005;23(2):133–148.
  • Erion MD, Cable EE, Ito BR, et al. Targeting thyroid hormone receptor-beta agonists to the liver reduces cholesterol and triglycerides and improves the therapeutic index. Proc Natl Acad Sci U S A. 2007;104(39):15490–15495.
  • Frank-Kamenetsky M, Grefhorst A, Anderson NN, et al. Therapeutic RNAi targeting PCSK9 acutely lowers plasma cholesterol in rodents and LDL cholesterol in nonhuman primates. Proc Natl Acad Sci U S A. 2008;105(33):11915–11920.
  • Stein CA, Cohen JS. Oligodeoxynucleotides as inhibitors of gene expression: a review. Cancer Res. 1988;48(10):2659–2668.

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