New clinical perspectives of hypolipidemic drug therapy in severe hypercholesterolemia

Current Medicinal Chemistry

Volumn 19, Issue 28, 2012, Pages 4861-4868

  Stefanutti, C ^a   Morozzi, C ^a   Di Giacomo, S ^a  

^a POLICLINICO UMBERTO I   (Italy)

Author keywords

Abetalipoproteinemia; Aortic valvular disease; Atherosclerosis; Combination lipid lowering drug therapy; Coronary artery disease; Familial hypercholesterolemia; HMGCoA reductase inhibitors; LDL receptor mutation; LDL apheresis; Lomitapide; Mipomersen; MTP inhibitors; Orthotopic liver transplantation; PCSK9 inhibitors; Severe hypercholesterolemia

Indexed keywords

ANTILIPEMIC AGENT; BILE ACID SEQUESTRANT; BMS 212122; COLESEVELAM; CP 346086; DIGOXIN; ETHINYLESTRADIOL; EZETIMIBE; FIBRIC ACID DERIVATIVE; GEMFIBROZIL; GLIPIZIDE; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE INHIBITOR; IMPLITAPIDE; JNJ 4506463; LEVONORGESTREL; LOMITAPIDE; LOW DENSITY LIPOPROTEIN CHOLESTEROL; LOW DENSITY LIPOPROTEIN RECEPTOR; MIPOMERSEN; NICOTINIC ACID; UNCLASSIFIED DRUG; WARFARIN;

AMINOTRANSFERASE BLOOD LEVEL; ARTICLE; CARDIOVASCULAR RISK; CREATININE BLOOD LEVEL; DISEASE SEVERITY; DIZZINESS; DOSE RESPONSE; DRUG BLOOD LEVEL; DRUG EFFICACY; DRUG MECHANISM; DRUG SAFETY; FLUSHING; GASTROINTESTINAL SYMPTOM; HOMOZYGOTE; HUMAN; HYPERCHOLESTEROLEMIA; IC 50; MONOTHERAPY; MYOPATHY; NONHUMAN; PRURITUS; SIDE EFFECT; TREATMENT INDICATION; TREATMENT RESPONSE; VASODILATATION;

CHOLESTEROL, LDL; HUMANS; HYDROXYMETHYLGLUTARYL COA REDUCTASES; HYDROXYMETHYLGLUTARYL-COA REDUCTASE INHIBITORS; HYPERCHOLESTEROLEMIA; HYPOLIPIDEMIC AGENTS; MICROSOMES; OLIGONUCLEOTIDES; PROPROTEIN CONVERTASES; RECEPTORS, LDL;

EID: 84870441966     PISSN: 09298673     EISSN: 1875533X     Source Type: Journal    
DOI: 10.2174/092986712803341485     Document Type: Article

References (89)

1. Goldstein, J.L.; Hobbs, H.H.; Brown, M.S. Familial hypercholesterolemia. In: Scriver CR, Beaudet AL, Sly WS, Valle D, eds. The Metabolic and Molecular Bases of Inherited Disease. 8th Ed. McGraw-Hill Information Services Company: New York, 2001, pp.2863-913
2. Hobbs, H.H.; Brown, M.S.; Goldstein, J.L. Molecular genetics of the LDL receptor gene in familial hypercholesterolemia. Hum. Mutat., 1992, 1, 445-6
3. Bertolini, S.; Cantafora, A.; Averna, M.; Cortese, C.; Motti, C.; Martini, S.; Pes, G.; Postiglione, A.; Stefanutti, C.; Blotta, I.; Pisciotta, L.; Rolleri, M.; Langheim, S.; Ghisellini, M.; Rabbone, I.; Calandra, S. Clinical expression of familial hypercholesterolemia in clusters of mutations of the LDL receptor gene that cause a receptor-defective or receptor-negative phenotype. Arteriosclerosis Thromb. Vasc. Biol., 2000, 20, 41-52
4. Gagne, C.; Gaudet, D.; Bruckert, E. Efficacy and safety of ezetimibe coadministered with atorvastatin or simvastatin in patients with homozygous familial hypercholesterolemia. Circulation, 2002, 105, 2469-75
5. Bilheimer, D.W. Portacaval shunt and liver transplantation in treatment of familial hypercholesterolemia. Arteriosclerosis, 1989, 9, 158-163
6. Forman, M.B.; Baker, S.G.; Mieny, C.J.; Joffe, B.I.; Sandler, M.P.; Mendelsohn, D.U.; Seftel, H.C. Treatment of homozygous familial hypercholesterolaemia with portacaval shunt. Atherosclerosis, 1982, 41, 349-61
7. Deckelbaum, R.J.; Lees, R.S.; Small, D.M.; Hedberg, S.E.; Grundy, S.M. Failure of complete bile diversion and oral bile acid therapy in the treatment of homozygous familial hypercholesterolemia. N. Engl. J. Med., 1977, 296, 465-70
8. Bilheimer, D.W.; Goldstein, J.L.; Grundy, S.M.; Starzl, T.E.; Brown, M.S. Liver transplantation to provide low-density-lipoprotein receptors and lower plasma cholesterol in a child with homozygous familial hypercholesterolemia. N. Engl. J. Med., 1984, 311, 1658-64
9. Starzl, T.E.; Bilheimer, D.W.; Bahnson, H.T.; Shaw, B.W. Jr., Hardesty, R.L.; Griffith, B.P.; Iwatsuki, S.; Zitelli, B.J.; Gartner, J.C. Jr.; Malatack, J.J. Heart-liver transplantation in a patient with familial hypercholesterolaemia. Lancet, 1984,1, 1382-3
10. Renz, J.F.; Kin, C.J.; Saggi, B.H.; Emond, J.C. Outcomes of living donor liver transplantation. In: Busuttil RW, Klintmalm GB, Eds. Transplantation of the Liver. Elsevier:Philadelphia, 2005, 47, pp.713-724
11. Nanashima, A.; Yamaguchi, H.; Shibasaki, S.; Ide, N.; Morino, S.; Sumida, Y.; Tsuji, T., Sawai, T., Nakagoe, T.;Nagayasu, T. Comparative analysis of postoperative morbidity according to type and extent of hepatectomy. Hepatogastroenterology, 2005, 52, 844-848
12. Umeshita, K.; Fujiwara, K.; Kiyosawa, K.; Makuuchi, M.; Satomi, S.; Sugimachi, K.; Tanaka, K.; Monden, M. Japanese Liver Transplantation Society. Operative morbidity of living liver donors in Japan. Lancet, 2003, 362, 687-690
13. Grossman, M.; Rader, D.J.; Muller, D.W.; Kolansky, D.M.; Kozarsky, K.; Clark, B.J. 3rd; Stein, E.A.; Lupien, P.J.; Brewer, H.B. Jr.; Raper, S.E. A pilot study of ex vivo gene therapy for homozygous familial hypercholesterolemia. Nat. Med., 1995, 1, 1148-54
14. Rader, D.J. Gene therapy for familial hypercholesterolemia. Nutr. Metab. Cardiovasc. Dis., 2001, 11, 40-44
15. Thompson, G.R. LDL apheresis. Atherosclerosis, 2003, 167, 1-13
16. Bosch, T. Therapeutic apheresis-state of the art in the year 2005. Ther. Apher. Dial., 2005, 9, 459-68
17. Executive Summary of The Third Report of The National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, And Treatment of High Blood Cholesterol In Adults (Adult Treatment Panel III). JAMA, 2001, 285, 2486-97
18. Szczepiorkowski, Z.M.; Winters, J.L.; Bandarenko, N.; Kim, H.C.; Linenberger, M.L.; Marques, M.B.; Sarode, R.; Schwartz, J.; Weinstein, R.; Shaz, B.H. Guidelines on the Use of Therapeutic Apheresis in Clinical Practice - Evidence-Based Approach from the Apheresis Applications Committee of the American Society for Apheresis. J. Clin. Apher., 2010, 25, 83-177
19. Thompson, G.R.; Maher, V.; Matthews, S.; Kitano, Y.; Neuwirth, C.; Shortt, M.B.; Davies, G.; Rees, A.; Mir, A.; Prescott, R.J. Familial Hypercholesterolaemia regression study: a randomised trial of low-density lipoprotein apheresis. Lancet, 1995, 345, 811-6
20. Tatami, R.; Inoue, N.; Itoh, H.; Kishino, B.; Koga, N.; Nakashima, Y.; Nishide, T.; Okamura, K.; Saito, Y.; Teramoto, T. Regression of coronary atherosclerosis by combined LDL-apheresis and lipid lowering therapy in patients with familial hypercholesterolemia: a multicenter study. The LAARS Investigators. Atherosclerosis, 1992, 95, 1-13
21. Aengevaren, W.R.; Kroon, A.A.; Stalenhoef, A.F.; Uijen, G.J.; Van der Werf, T. LDL apheresis improves regional myocardial perfusion in patients with hypercholesterolemia and extensive coronary artery disease. LDLapheresis Atherosclerosis Regression Study (LAARS). J. Am. Coll. Cardiol., 1996, 28, 1696-1704
22. Stefanutti, C.; Vivenzio, A.; Di Giacomo, S.; Mazzarella, B.; Bosco, G.; Berni, A. Aorta and Coronary Angiographic Follow-up of Children with Severe Hypercholesterolemia Treated with LDL Apheresis. Transfusion, 2009, 49, 1461-1470
23. Garcia, C.K.; Wilund, K.; Arca, M.; Zuliani, G.; Fellin, R.; Maioli, M.; Calandra, S.; Bertolini, S.; Cossu, F.; Grishin, N.; Barnes, R.; Cohen, J.C.; Hobbs, H.H. Autosomal recessive hypercholesterolemia caused by mutations in a putative LDL receptor adaptor protein. Science, 2001, 292, 1394-8
24. Benlian, P.; De Gennes, J.; Foubert, L.; Zhang, H.; Gagne, S.; Hayden, M. Premature atherosclerosis in patients with familial chylomicronemia caused by mutations in the lipoprotein lipase gene. N. Engl. J. Med. 1996, 335, 848-54
25. Rubinsztein, D.C.; Raal, F.J.; Seftel, H.C.; Pilcher, G.; Coetzee, G.A.; Van der Westhuyzen, D.R. Characterization of six patients who are double heterozygotes for familial hypercholesterolemia and familial defective apo B-100. Arterioscler. Thromb., 1993, 13, 1076-81
26. Pearson, T.A.; Laurora, I.; Chu, H.; Kafonek, S. The Lipid Treatment Assessment Project (L-TAP): a multicenter survey to evaluate the percentages of dyslipidemic patients receiving lipid-lowering therapy and achieving lowdensity lipoprotein cholesterol goals. Arch. Intern. Med., 2000, 160, 459-467
27. Bays, H. Ezetimibe. Expert. Opin. Investig. Drugs, 2002, 11, 1587-1604
28. Catapano, A.L. Ezetimibe: a selective inhibitor of cholesterol absorption. Eur. Heart J. Suppl., 2001, 3, 6-10
29. Gagné, C.; Bays, H.E.; Weiss, S.R., Mata, P.; Quinto, K.; Melino, M.; Cho, M.; Musliner, T.A.; Gumbiner, B.; for the Ezetimibe Study Group. Efficacy and safety of ezetimibe added to ongoing statin therapy for treatment of patients with primary hypercholesterolemia. Am. J. Cardiol., 2002, 90, 1084-1091
30. Knopp, R.H.; Tsunehara, C.; Retzlaff, B.M.; Fish, B.; Nguyen, H.; Anderson, S.; Nguyen, T. Lipoprotein effects of combined ezetimibe and colesevelam hydrochloride versus ezetimibe alone in hypercholesterolemic subjects: a pilot study. Metab. - Clin. Exper., 2006, 55, 1697-1703
31. Bays, H.; Rhyne, J.; Abby, S.; Lai, Y.L.; Jones, M. Lipid-lowering effects of colesevelam HCl in combination with ezetimibe. Curr. Med. Res. Opin., 2006, 22, 2191-2200
32. Rivers, S.M.; Kane, M.P.; Busch, R.S.; Bakst, G.; Hamilton, R.A. Colesevelam Hydrochloride-Ezetimibe Combination Lipid-Lowering Therapy in Patients with Diabetes or Metabolic Syndrome and a History of Statin Intolerance. Endocr. Pract., 2007, 13, 11-16
33. McKenney, J.M.; Farnier, M.; Lo, K.W.; Bays, H.E.; Perevozkaya, I.; Carlson, G.; Davies, M.J.; Mitchel, Y.B.; Gumbiner, B. Safety and efficacy of long-term co-administration of fenofibrate and ezetimibe in patients with mixed hyperlipidemia. J. Am. Coll. Cardiol., 2006, 47, 1584-7
34. Kosoglou, T.; Statkevich, P.; Johnson-Levonas, A.O.; Paolini, J.F.; Bergman, A.J.; Alton, K.B. Ezetimibe: a review of its metabolism, pharmacokinetics and drug interactions. Clin. Pharmacokinet., 2005, 44, 467-94
35. Frick, M.H.; Elo, O.; Haapa, K.; Heinonen, O.P.; Heinsalmi, P.; Helo, P.; Huttunen, J.K.; Kaitaniemi, P.; Koskinen, P.; Manninen, V.; Mäenpää, H.; Mälkönen, M.; Mänttäri, M.; Norola, S.; Pasternack, A.; Pikkarainen, J.; Romo, M.; Sjöblom, T.; Nikkilä, E.A. Helsinki Heart Study: primaryprevention trial with gemfibrozil in middle-aged men with dyslipidemia. Safety of treatment, changes in risk factors, and incidence of coronary heart disease. N. Engl. J. Med. 1987, 317, 1237-1245
36. Manninen, V.; Tenkanen, L.; Koskinen, P.; Huttunen, J.K.; Mänttäri, M.; Heinonen, O.P.; Frick, M.H. Joint effects of serum triglyceride and LDL cholesterol and HDL cholesterol concentrations on coronary heart disease risk in the Helsinki Heart Study: implications for treatment. Circulation, 1992, 85, 37-45
37. Rubins, H.B.; Robins, S.J.; Collins, D.; Fye, C.L.; Anderson, J.W.; Elam, M.B.; Faas, F.H.; Linares, E.; Schaefer, E.J.; Schectman, G.; Wilt, T.J.; Wittes, J.; for the Veterans Affairs High-Density Lipoprotein Cholesterol Intervention Trial Study Group. Gemfibrozil for the secondary prevention of coronary heart disease in men with low levels of high-density lipoprotein cholesterol. N. Engl. J. Med. 1999, 341, 410-418
38. Abifadel, M.; Varret, M.; Rabes, J.P.; Allard, D.; Ouguerram, K.; Devillers, M.; Cruaud, C.; Benjannet, S.; Wickham, L.; Erlich, D.; Derré, A.; Villéger, L.; Farnier, M.; Beucler, I.; Bruckert, E.;, Chambaz, J.; Chanu, B.; Lecerf, J.M.; Luc, G.; Moulin, P., Weissenbach, J.; Prat, A.; Krempf, M.; Junien, C.; Seidah, N.G.; Boileau, C. Mutations in PCSK9 cause autosomal dominant hypercholesterolemia. Nat. Genet., 2003, 34, 154-6
39. Maxwell, K.N.; Breslow, J.L. Adenoviral-mediated expression of Pcsk9 in mice results in a low-density lipoprotein receptor knockout phenotype. Proc. Natl. Acad. Sci., 2004, 101, 7100-5
40. Park, S.W.; Moon, Y.A.; Horton, J.D. Post-transcriptional regulation of low density lipoprotein receptor protein by proprotein convertase subtilisin/kexin type 9a in mouse liver. J. Biol. Chem. 2004, 279, 50630-8
41. Lambert, G.; Charlton, F.; Rye, K.A.; Piper, D.E. Molecular basis of PCSK9 function. Atherosclerosis, 2009, 203, 1-7
42. Zhang, D.W.; Lagace, T.A.; Garuti, R.; Zhao, Z.; McDonald, M.; Horton, J.D.; Cohen, J.C.; Hobbs, H.H. 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, 18602-12
43. Li, J.; Tumanut, C.; Gavigan, J.A.; Huang, W.J.; Hampton, E.N.; Tumanut, R.; Suen, K.F.; Trauger, J.W.; Spraggon, G.; Lesley, S.A.; Liau, G.; Yowe, D.; Harris, J.L. Secreted PCSK9 promotes LDL receptor degradation independently of proteolytic activity. Biochem. J., 2007, 406, 203-7
44. Zhang, D.W.; Garuti, R.; Tang, W.J.; Cohen, J.C.; Hobbs, H.H. Structural requirements for PCSK9-mediated degradation of the low-density lipoprotein receptor. Proc. Natl. Acad. Sci., 2008, 105, 13045-50
45. Innerarity, T.L.; Weisgraber, K.H.; Arnold, K.S.; Mahley, R.W.; Krauss, R.M.; Vega, G.L.; Grundy, S.M. Familial defective apolipoprotein B-100: low density lipoproteins with abnormal receptor binding. Proc. Natl. Acad. Sci., 1987, 84, 6919-23
46. Kwon, H.J.; Lagace, T.A.; McNutt, M.C.; Horton, J.D., Deisenhofer, J. Molecular basis for LDL receptor recognition by PCSK9. Proc. Natl. Acad. Sci., 2008, 105, 1820-5
47. Seidah, N.G., Prat, A. The proprotein convertases are potential targets in the treatment of dyslipidemia. J. Mol. Med., 2007, 85, 685-696
48. Seidah, N.G. PCSK9 as a therapeutic target of dyslipidemia. Expert. Opin. Ther. Targets. 2009, 13, 19-28
49. Abifadel, M.; Pakradouni, J.; Collin, M.; Samson-Bouma, M.E.; Varret, M.; Rabès, J.P.; Boileau, C. Strategies for proprotein convertase subtilisin kexin 9 modulation: a perspective on recent patents. Expert Opin. Ther. Pat., 2010, 20, 1547-71
50. Duff, C.J.; Hooper, N.M. PCSK9: an emerging target for treatment of hypercholesterolemia. Expert Opin. Ther. Targets., 2011, 15, 157-168
51. Rashid, S.; Curtis, D.E.; Garuti, R.; Anderson, N.N.; Bashmakov, Y.; Ho, Y.K.; Hammer, R.E.; Moon, Y.A.; Horton, J.D. Decreased plasma cholesterol and hypersensitivity to statins in mice lacking Pcsk9. Proc. Natl. Acad. Sci., 2005, 102, 5374-9
52. Zhao, Z.; Tuakli-Wosornu, Y.; Lagace, T.A.; Kinch, L.; Grishin, N.V.; Horton, J.D.; Cohen, J.C.; Hobbs, H.H. Molecular characterization of lossof-function mutations in PCSK9 and identification of a compound heterozygote. Am. J. Hum. Genet., 2006, 79, 514-23
53. Cariou, B.; Ouguerram, K.; Zaïr, Y.; Guerois, R.; Langhi, C.; Kourimate, S.; Benoit, I.; Le May, C.; Gayet, C.; Belabbas, K.; Dufernez, F.; Chétiveaux, M.; Tarugi, P.; Krempf, M.; Benlian, P.; Costet, P.; PCSK9 dominant negative mutant results in increased LDL catabolic rate and familial hypobetalipoproteinemia. Arterioscler. Thromb. Vasc. Biol., 2009, 29, 2191-7
54. Hooper, A.J.; Marais, A.D.; Tanyanyiwa, D.M.; Burnett, J.R. The C679X mutation in PCSK9 is present and lowers blood cholesterol in a Southern African population. Atherosclerosis, 2007, 193, 445-8
55. Strøm, T.B.; Holla, ø.L.; Cameron, J.; Berge, K.E.; Leren, T.P. Loss-offunction mutation R46L in the PCSK9 gene has little impact on the levels of total serum cholesterol in familial hypercholesterolemia heterozygotes. Clinica Chimica Acta, 2010, 411, 229-233
56. Mayne, J.; Dewpura, T.; Raymond, A.; Cousins, M.; Chaplin, A.; Lahey, K.A.; LaHaye, S.A.; Mbikay, M.; Ooi, T.C.; Chrétien, M. Plasma PCSK9 levels are significantly modified by statins and fibrates in humans. Lipids Health Dis., 2008, 11, 7-22
57. Chan, J.C.; Piper, D.E.; Cao, Q.; Liu, D.; King, C.; Wang, W.; Tang, J.; Liu, Q.; Higbee, J.; Xia, Z.; Di, Y.; Shetterly, S.; Arimura, Z.; Salomonis, H.; Romanow, W.G.; Thibault, S.T.; Zhang, R.; Cao, P.; Yang, X.P.; Yu, T.; Lu, M.; Retter, M.W.; Kwon, G.; Henne, K.; Pan, O.; Tsai, M.M.; Fuchslocher, B.; Yang, E.; Zhou, L.; Lee, K.J.; Daris, M.; Sheng, J.; Wang, Y.; Shen, W.D.; Yeh, W.C.; Emery, M.; Walker, N.P.; Shan, B.; Schwarz. M.; Jackson, S.M. A proprotein convertase subtilisin/kexin type 9 neutralizing antibody reduces serum cholesterol in mice and nonhuman primates. Proc. Natl. Acad. Sci. USA, 2009, 106, 9820-9825
58. Frank-Kamenetsky, M.; Grefhorst, A.; Anderson, N.N.; Racie, T.S.; Bramlage, B.; Akinc, A.; Butler, D.; Charisse, K.; Dorkin, R.; Fan, Y.; Gamba- Vitalo, C.; Hadwiger, P.; Jayaraman, M.; John, M.; Jayaprakash, K.N.; Maier, M.; Nechev, L.; Rajeev, K.G.; Read, T.; Röhl, I.; Soutschek, J.; Tan, P.; Wong, J.; Wang, G.; Zimmermann, T.; de Fougerolles, A.; Vornlocher, H.P.; Langer, R.; Anderson, D.G.; Manoharan, M.; Koteliansky, V.; Horton, J.D.; Fitzgerald, K. Therapeutic RNAi targeting PCSK9 acutely lowers plasma cholesterol in rodents and LDL cholesterol in nonhuman primates. Proc. Natl. Acad. Sci. USA, 2008, 19, 11915-20
59. Ni, Y.G.; Condra, J.H.; Orsatti, L.; Shen, X.; Di Marco, S.; Pandit, S.; Bottomley, M.J.; Ruggeri, L.; Cummings, R.T.; Cubbon, R.M.; Santoro, J.C.; Ehrhardt, A.; Lewis, D.; Fisher, T.S.; Ha, S.; Njimoluh, L.; Wood, D.D.; Hammond, H.A.; Wisniewski, D.; Volpari, C.; Noto, A.; Lo Surdo, P.; Hubbard, B.; CarfÍ, A.; Sitlani, A. A proprotein convertase subtilisin-like/kexin type 9 (PCSK9) C-terminal domain antibody antigen-binding fragment inhibits PCSK9 internalization and restores low density lipoprotein uptake. J. Biol. Chem., 2010, 285, 12882-91
60. Berge, K.E.; Ose, L.; Leren, T.P. Missense mutations in the PCSK9 gene are associated with hypocholesterolemia and possibly increased response to statin therapy. Arterioscler. Thromb. Vasc. Biol., 2006, 26, 1094-100
61. Thompson, J.F.; Hyde, C.L.; Wood, L.S.; Paciga, S.A.; Hinds, D.A.; Cox, D.R.; Hovingh, G.K.; Kastelein, J.J. Comprehensive whole-genome and candidate gene analysis for response to statin therapy in the Treating to New Targets (TNT) cohort. Circ. Cardiovasc. Genet., 2009, 2, 173-81
62. Konrad, R.J.; Troutt, J.S.; Cao, G. Effects of currently prescribed LDL-Clowering drugs on PCSK9 and implications for the next generation of LDLC-lowering agents. Lipids Health Dis., 2011, 10, 38
63. Crooke, R.M.; Graham, M.J.; Lemonidis, K.M.; Whipple, C.P.; Koo, S,; Perera, R.J. An apolipoprotein B antisense oligonucleotide lowers LDL cholesterol in hyperlipidemic mice without causing hepatic steatosis. J. Lipid. Res., 2005, 46, 872-84
64. Burnett, J.R. Drug evaluation: ISIS-301012, an antisense oligonucleotide for the treatment of hypercholesterolemia. Curr. Opin. Mol. Ther., 2006, 8, 461-67
65. Crooke, R.; Baker, B.; Wedel, M. Cardiovascular therapeutic applications. In: Crooke ST, editor. Antisense Drug Technology; Principles, Strategies and Applications. 2nd edition. Boca Raton, FL: CRC Press. 2007, 601-39
66. Sankatsing, R.R.; Fouchier, S.W.; de Haan, S.; Hutten, B.A.; de Groot, E.; Kastelein, J.J.; Stroes, E.S. Hepatic and cardiovascular consequences of familial hypobetalipoproteinemia. Arterioscler. Thromb. Vasc. Biol., 2005, 25, 1979-84
67. Kastelein, J.J.; Wedel, M.K.; Baker, B.F.; Su, J.; Bradley, J.D.; Yu, R.Z.; Chuang, E.; Graham, M.J.; Crooke, R.M. Potent reduction of apolipoprotein B and LDL cholesterol by short-term administration of an antisense inhibitor of apolipoprotein B. Circulation, 2006, 114, 1729-35
68. Yu, R.Z.; Geary, R.S.; Flaim, J.; Riley, G.C.; Tribble, D.L.; vanVliet, A.A.; Wedel, M.K. Lack of pharmacokinetic interaction for ISIS 301012, a 2'-Omethoxyethyl modified antisense oligonucleotide targeting apoB-100 mRNA, with oral lipid-lowering agents, simvastatin and ezetimibe, when coadministered in healthy human subjects. Clin, Pharmacokinet., 2009, 48, 39-50
69. Yu, R.Z.; Kim, T.W.; Hong, A.; Watanabe, T.A.; Gaus, H.J.; Geary, R.S. Cross-species pharmacokinetic comparison from mouse to man of a second generation antisense oligonucleotide ISIS 301012, targeting human Apo B-100. Drug. Metab. Dispos. 2007, 35, 460-8
70. Rader, D.J.; Brewer, H.B. Jr. Abetalipoproteinemia. New insights into lipoprotein assembly and vitamin E metabolism from a rare genetic disease. JAMA , 1993, 270, 865-9
71. Berriot-Varoqueaux, N.; Aggerbeck, L.P.; Samson-Bouma, M.; Wetterau, J.R. The role of the microsomal triglygeride transfer protein in abetalipoproteinemia. Annu. Rev. Nutr., 2000, 20, 663-97
72. Wetterau, J.R.; Aggerbeck, L.P.; Bouma, M.E.; Eisenberg, C.; Munck, A.; Hermier, M.; Schmitz, J.; Gay, G:; Rader, D.J.; Gregg, R.E. Absence of microsomal triglyceride transfer protein in individuals with abetalipoproteinemia. Science, 1992, 258, 999-1001
73. Sharp, D.; Blinderman, L.; Combs, K.A.; Kienzle, B.; Ricci, B.; Wager-Smith, K.; Gil, C.M.; Turck, C.W.; Bouma, M.E.; Rader, D.J. Cloning and gene defects in microsomal triglyceride transfer protien associated with abetalipoproteinemia. Nature, 1993, 365, 65-9
74. Raabe, M.; Flynn, L.M.; Zlot, C.H.; Wong, J.S.; Véniant, M.M.; Hamilton, R.L.; Young, S.G. Knockout of the abetalipoproteinemia gene in mice: reduced lipoprotein secretion in heterozygotes and embryonic lethality in homozygotes. Proc. Natl. Acad. Sci. USA, 1998, 95, 8686-91
75. Raabe, M.; Véniant, M.M.; Sullivan, M.A.; Zlot, C.H.; Björkegren, J.; Nielsen, L.B.; Wong, J.S.; Hamilton, R.L.; Young, S.G. Analysis of the role of microsomal trig lyceride transfer protein in the liver of tissue-specific knockout mice. J. Clin. Invest., 1999, 103, 1287-98
76. Cuchel, M.; Bloedon, L.T.; Szapary, P.O.; Kolansky, D.M.; Wolfe, M.L.; Sarkis, A.; Millar, J.S.; Ikewaki, K.; Siegelman, E.S.; Gregg, R.E.; Rader, D.J. "Inhibition of Microsomal Triglyceride Transfer Protein in Familial Hypercholesterolemia". N. Engl. J. Med., 2007, 356, 148-56
77. Li, J.; Bertinato, P.; Cheng, H.; Cole, B.M.; Bronk, B.S.; Jaynes, B.H.; Hickman, A.; Haven, M.L.; Kolosko, N.L.; Barry, C.J.; Manion, T.B. Discovery of potent and orally active MTP inhibitors as potential anti-obesity agents. Bioorg. Med. Chem. Lett., 2006, 16, 3039-3042
78. Grundy, S.M.; Cleeman, J.I.; Merz, C.N.; Brewer, H.B. Jr.; Clark, L.T.; Hunninghake, D.B.; Pasternak, R.C.; Smith, S.C. Jr.; Stone, N.J.; National Heart, Lung, and Blood Institute; American College of Cardiology Foundation; American Heart Association. Implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III Guidelines. Circulation, 2004, 110, 227-39
79. Prospective Studies Collaboration; Lewington, S.; Whitlock, G.; Clarke, R.; Sherliker, P.; Emberson, J.; Halsey, J.; Qizilbash, N.; Peto, R.; Collins, R. Blood cholesterol and vascular mortality by age, sex, and blood pressure: a meta-analysis of individual data from 61 prospective studies with 55000 vascular deaths. Lancet, 2007, 370, 1829-39
80. Davidson, M.H.; Robinson, J.G. Safety of aggressive lipid management. J. Am. Coll. Cardiol. 2007, 49, 1753-62
81. O'Keefe, J.H.; Cordain, L.; Harris, W.H.; Moe, R.M.; Vogel, R. Optimal low-density lipoprotein is 50 to 70 mg/dl. J. Am. Coll. Cardiol., 2004, 43, 2142-6
82. Costet, P. Molecular pathways and agents for lowering LDL-cholesterol in addition to statins. Pharmacol. Ther., 2010, 126, 3, 263-78
83. Brown, W.V.; Bays, H.; Davidson, M.; Goldberg, A. Drugs in development for management of lipoprotein disorders. J. Clin. Lipidol., 2011, 5, 66-75
84. Horton, J.D.; Cohen, J.C.; Hobbs, H.H. PCSK9: A convertase that coordinates LDL catabolism. J. Lipid Res., 2009, 50, S172-S177
85. Steinberg, D.; Witztum, J.L. Inhibition of PCSK9: A powerful weapon for achieving ideal LDL cholesterol levels. PNAS, 2009, 106, 9546-9547
86. Visser, M.E.; Kastelein, J.J.; Stroes, E.S. Apolipoprotein B synthesis inhibition: results from clinical trials. Curr. Opin. Lipidol., 2010, 21, 319-323
87. Samaha, F.F.; McKenney J.; Bloedon L.T.; Sasiela J.W.; Rader D.J. "Impact of the MTP-Inhibitor, AEGR-733, as Monotherapy and in Combination with Ezetimibe on Lipid Subfractions as Measured by NMR Spectroscopy". Circulation, 2008, 118, 5, 469
88. Chandler, C.E.; Wilder, D.E.; Pettini, J.L.; Savoy, Y.E.; Petras, S.F.; Chang, G.; Vincent, J.; Harwood, H.J. Jr. CP-346086: an MTP inhibitor that lowers plasma cholesterol and triglycerides in experimental animals and in humans. J. Lipid Res., 2003, 44, 1887-1901.
89. Parasassi T, Brunelli R, Bracci-Laudiero L, Greco G, Gustafsson AC, Krasnowska EK, Lundebrg J, Lundeberg T, Pittaluga E, Romano MC, Serafino A. Differentiation of normal and cancer cells induced by sulfhydryl reduction : biochemical and molecular mechanisms. Cell Death Differ., 2005; 12(10): 1285-96.