Therapeutic approaches to drug targets in hyperlipidemia

BioMedicine (Netherlands)

Volumn 2, Issue 4, 2012, Pages 137-146

  Mahamuni, Sagar P ^a   Khose, Rekha D ^a   Menaa, Farid ^b   Badole, Sachin L ^a  

^a Affiliated to Savitribai Phule Pune University   (India)

^b Fluorotronics Inc   (United States)

Author keywords

Drug targets; Hyperlipidemia; Lanosterol synthase inhibitors; Squalene synthase inhibitors

Indexed keywords

ANTILIPEMIC AGENT; APOLIPOPROTEIN B; ATORVASTATIN; CHOLESTEROL ABSORPTION INHIBITOR; CHOLESTEROL ESTER TRANSFER PROTEIN INHIBITOR; CHOLESTEROL O ACYLTRANSFERASE INHIBITOR; CHYLOMICRON; COLESEVELAM; COLESTIPOL; COLESTYRAMINE; DIACYLGLYCEROLACYLTRANSFERASE INHIBITOR; EZETIMIBE; FIBRIC ACID DERIVATIVE; FLUINDOSTATIN; HIGH DENSITY LIPOPROTEIN; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE INHIBITOR; LANOSTEROL SYNTHASE INHIBITOR; LAPAQUISTAT; LOW DENSITY LIPOPROTEIN CHOLESTEROL; MEVINOLIN; N (2,6 DIISOPROPYLPHENYL)TETRADECYLTHIOACETAMIDE; OMEGA 3 FATTY ACID; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR AGONIST; PRAVASTATIN; SIMVASTATIN; SQUALENE SYNTHASE INHIBITOR; THYROID HORMONE DERIVATIVE; TRIACYLGLYCEROL; UNCLASSIFIED DRUG; UNINDEXED DRUG; VERY LOW DENSITY LIPOPROTEIN;

ABDOMINAL PAIN; ALANINE AMINOTRANSFERASE BLOOD LEVEL; ARTHRALGIA; ASPARTATE AMINOTRANSFERASE BLOOD LEVEL; ATHEROSCLEROSIS; BACKACHE; BLEEDING; CARDIOVASCULAR DISEASE; CATARACT; COGNITIVE DEFECT; DIARRHEA; DIGESTION; DISEASE ASSOCIATION; DRUG TARGETING; DRY SKIN; ENVIRONMENTAL FACTOR; FAMILIAL COMBINED HYPERLIPIDEMIA; FLATULENCE; GALLSTONE; GASTROINTESTINAL TOXICITY; GENETICS; HEADACHE; HEALTH HAZARD; HEART ARRHYTHMIA; HEMORRHOIDAL BLEEDING; HUMAN; HYPERCHOLESTEROLEMIA; HYPERLIPIDEMIA; HYPERTRIGLYCERIDEMIA; INSULIN RESISTANCE; LIPID METABOLISM; METABOLIC SYNDROME X; MYALGIA; MYOPATHY; MYOSITIS; OBESITY; PRIORITY JOURNAL; REVIEW; RHABDOMYOLYSIS; SIDE EFFECT; SINUSITIS; TOXIC HEPATITIS; TRIACYLGLYCEROL BLOOD LEVEL; UNSPECIFIED SIDE EFFECT;

EID: 84871609281     PISSN: 22118020     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.biomed.2012.08.002     Document Type: Review

References (122)

1. Kolovou G.D., Anagnostopoulou K.K., Cokkinos D.V. Pathophysiology of dyslipidemia in the metabolic syndrome. Postgrad Med J 2005, 81:358-366.
2. Bernard J. Free fatty acid receptor family: novel targets for the treatment of diabetes and dyslipidemia. Curr Opin Investig Drugs 2008, 9:1078-1083.
3. Funatsu T., Suzuki K., Goto M., Arai Y., Kakuta H., Tanaka H., et al. Prolonged inhibition of cholesterol synthesis by atorvastatin inhibits apo B-100 and triglyceride secretion from HepG2 cells. Atherosclerosis 2001, 157:107-115.
4. Micallef M.A., Garg M.L. Beyond blood lipids: phytosterols, statins and omega-3 polyunsaturated fatty acid therapy for hyperlipidemia. J Nutr Biochem 2009, 20:927-939.
5. Gordon T., Kannel W.B. Premature mortality from coronary heart disease. The Framingham study. JAMA 1971, 215:1617-1625.
6. Holvoet P., Jenny N.S., Schreiner P.J., Tracy R.P., Jacobs D.R. The relationship between oxidized LDL and other cardiovascular risk factors and subclinical CVD in different ethnic groups: the Multi-Ethnic Study of Atherosclerosis (MESA). Atherosclerosis 2007, 194:245-252.
7. Foley K.A., Vasey J., Alexander C.M., Markson L.E. Development and validation of the Hyperlipidemia Attitudes and Beliefs In Treatment (HABIT) survey for physicians. J Gen Intern Med 2003, 18:984-990.
8. Lipid management guideline. National Heart Foundation of Australia, The Cardiac Society of Australia and New Zealand. Med J Aust 2001, 175(Suppl):S57-S85. NHFA.
9. Fonseca V. The metabolic syndrome, hyperlipidemia and insulin resistance. Clin Cornerstone 2005, 7:61-72.
10. Ginsberg H.N., Huang L.S. The insulin resistance syndrome: impact on lipoprotein metabolism and atherothrombosis. J Cardiovasc Risk 2000, 7:325-331.
11. Genest J.G. Dyslipidemia and coronary artery disease. Can J Cardiol 2000, 16(Suppl. A). 3A-4A.
12. Ninomiya J.K., L'Italien G., Criqui M.H., Whyte J.L., Gamst A., Chen R.S. Association of the metabolic syndrome with history of myocardial infarction and stroke in the Third National Health and Nutrition Examination Survey. Circulation 2004, 109:42-46.
13. Anderson J.L., Horne B.D., Jones H.U., Reyna S.P., Carlquist J.F., Bair T.L., et al. For the intermountain heart collaborative (IHC) study. Which features of the metabolic syndrome predict the prevalence and clinical outcomes of angiographic coronary artery disease?. Cardiology 2004, 101:185-193.
14. Halpern A., Mancini M., Maghalhães M.E., Fisberg M., Radominski R., Bertolami M.C., et al. Metabolic syndrome, dyslipidemia, hypertension and type 2 diabetes mellitus in youth, from diagnosis to treatment. Diabetol Metab Syndr 2010, 55:1-20.
15. Steinberger J., Daniels S.R., Eckel R.H., Hayman L., Lustig R.H., McCrindle B. Progress and challenges in metabolic syndrome in children and adolescents: a scientific statement from the American Heart Association Atherosclerosis, Hypertension, and Obesity in the Young Committee of the Council on Cardiovascular Disease in the Young; Council on Cardiovascular Nursing; and Council on Nutrition, Physical Activity, and Metabolism. Circulation 2009, 119:628-647.
16. Executive summary of the third report of National Cholesterol Education Program (NCEP) expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (Adult Treatment Panel III). JAMA 2001, 285:2486-2497.
17. McCrindle B.W., Ose L., Marais A.D. Efficacy and safety of atorvastatin in children and adolescents with familial hypercholesterolemia or severe hyperlipidemia: a multicenter, randomized, placebo-controlled trial. J Pediatr 2003, 143:74-80.
18. Iqbal J., Hussain M.M. Intestinal lipid absorption. Am J Physiol Endocrinol Metab 2009, 296:E1183-E1194.
19. Lien E.L. The role of fatty acid composition and positional distribution in fat absorption in infants. J Pediatr 1994, 125:S62-S68.
20. Carlier H., Bernard A., Caselli C. Digestion and absorption of polyunsaturated fatty acids. Reprod Nutr Dev 1991, 31:475-500.
21. Ramírez M., Amate L., Gil A. Absorption and distribution of dietary fatty acids from different sources. Early Human Development 2001, 65(Suppl.):S95-S101.
22. Hernell O., Bläckberg L. Digestion of human milk lipids: physiological significance of sn-2 monoacylglycerol hydrolysis by salt-stimulated lipase. Pediatr Res 1982, 16:882-885.
23. Jain K.S., Kathiravan M.K., Somania R.S., Shishoo C.J. The biology and chemistry of hyperlipidemia. Bioorg Med Chem 2007, 15:4674-4699.
24. Capell W.H., Spiegelman K.P., Eckel R.H. Therapeutic targets in severe hypertriglyceridemia. Drug Disc Today: Dis Mech 2004, 1:171-177.
25. Athyros V.G., Giouleme O.I., Nikolaidis N.L., Vasiliadis T.V., Bouloukos V.I., Kontopoulos A.G., et al. Long-term follow-up of patients with acute hypertriglyceridemia- induced pancreatitis. J Clin Gastroenterol 2002, 34:472-475.
26. Pejic R.N., Lee D.T. Hypertriglyceridemia. J Am Board Fam Med 2006, 19:310-316.
27. Hopkins P.N., Heiss G., Ellison R.C., Province M.A., Pankow J.S., Eckfeldt J.H., et al. Coronary artery disease risk in familial combined hyperlipidemia and familial hypertriglyceridemia: a case-control comparison from the National Heart, Lung, and Blood Institute Family Heart Study. Circulation 2003, 108:519-523.
28. Bersot T., Haffner S., Harris W.S., Kellick K.A., Morris C.M. Hypertriglyceridemia: management of atherogenic dyslipidemia. J Fam Pract 2006, 55:S1-S8.
29. Feoli-Fonseca J.C., Lévy E., Godard M., Lambert M. Familial lipoprotein lipase deficiency in infancy: clinical, biochemical, and molecular study. J Pediatr 1998, 133:417-423.
30. Francis A., Levy Y. Chylomicronemia syndrome. Harefuah 2002, 14:201-203.
31. Dunbar R.L., Rader D.J. Demystifying triglycerides: a practical approach for the clinician. Cleve Clin J Med 2005, 72:661-680.
32. Bhatnagar D., Soran H., Durrington P.N. Hypercholesterolemia and its management. BMJ 2008, 337:503-508.
33. Jia L., Fu M., Tian Y., Xu Y., Gou L., Tian H., et al. Alterations of high-density lipoprotein subclasses in hypercholesterolemia and combined hyperlipidemia. Int J Cardiol 2007, 120:331-337.
34. Department of Health National service framework for coronary heart disease 2000, DoH, London.
35. Orsó E., Ahrens N., Kilalić D., Schmitz G. Familial hypercholesterolemia and lipoprotein(a) hyperlipidemia as independent and combined cardiovascular risk factors. Atheosclerosis Suppl 2009, 10:74-78.
36. Bhatnagar D. Diagnosis and screening for familial hypercholesterolemia: finding the patient, finding the genes. Ann Clin Biochem 2006, 43:441-456.
37. Lambert G., Charlton F., Rye K.A., Piper D.E. Molecular basis of PCSK9 function. Atherosclerosis 2009, 203:1-7.
38. Hopkins P.N. Familial hypercholesterolemia-improving treatment and meeting guidelines. Int J Cardiol 2003, 89:13-23.
39. de Graaf J., van der Vleuten G.M., ter Avest E., Dallinga-Thie G.M., Stalenhoef A.F. High plasma level of remnant-like particles cholesterol in familial combined hyperlipidemia. J Clin Endocrinol Metab 2007, 92:1269-1275.
40. Brunzell J.D., Schrott H.G., Motulsky A.G., Bierman E.L. Myocardial infarction in the familial forms of hypertriglyceridemia. Metabolism 1976, 25:313-320.
41. de Graaf J., Veerkamp M.J., Stalenhoef A.F. Metabolic pathogenesis of familial combined hyperlipidaemia with emphasis on insulin resistance, adipose tissue metabolism and free fatty acids. J R Soc Med 2002, 95:46-53.
42. Kieffer T.J., Habener J.F. The adipoinsular axis: effects of leptin on pancreatic beta-cells. Am J Physiol Endocrinol Metab 2000, 278:E1-14.
43. Considine R.V., Sinha M.K., Heiman M.L., Kriauciunas A., Stephens T.W., Nyce M.R., et al. Serum immunoreactive leptin concentrations in normal-weight and obese humans. N Engl J Med 1996, 334:292-295.
44. Melloul D., Marshak S., Cerasi E. Regulation of insulin gene transcription. Diabetologia 2002, 45:309-326.
45. van der Vleuten G.M., Veerkamp M.J., van Tits L.J., Toenhake H., den Heijer M., Stalenhoef A.F., et al. Elevated leptin levels in subjects with familial combined hyperlipidemia are associated with the increased risk for CVD. Atherosclerosis 2005, 183:355-360.
46. Grundy S.M. Low-density lipoprotein, non-high-density lipoprotein, and apolipoprotein B as targets of lipid-lowering therapy. Circulation 2002, 106:2526-2529.
47. Frost P.H., Havel R.J. Rationale for use of non-high-density lipoprotein cholesterol rather than low-density lipoprotein cholesterol as a tool for lipoprotein cholesterol screening and assessment of risk and therapy. Am J Cardiol 1998, 81:26B-31B.
48. Karpe F., Hamsten A. Postprandial lipoprotein metabolism and atherosclerosis. Curr Opin Lipidol 1995, 6:123-129.
49. Karpe F., Taskinen M.R., Nieminen M.S., Frick M.H., Kesäniemi Y.A., Pasternack A., et al. Remnant-like lipoprotein particle cholesterol concentration and progression of coronary and vein-graft atherosclerosis in response to gemfibrozil treatment. Atherosclerosis 2001, 157:181-187.
50. ter Avest E., Holewijn S., Bredie S.J., Stalenhoef A.F., de Graaf J. Remnant particles are the major determinant of an increased intima media thickness in patients with familial combined hyperlipidemia (FCH). Atherosclerosis 2007, 191:220-226.
51. Austin M.A., Brunzell J.D., Fitch W.L., Krauss R.M. Inheritance of low density lipoprotein subclass patterns in familial combined hyperlipidemia. Arteriosclerosis 1990, 10:520-530.
52. Cortner J.A., Coates P.M., Bennet M.J., Cryer D.R., Le N.A. Familial combined hyperlipidaemia: use of stable isotopes to demonstrate overproduction of very low-density lipoprotein apolipoprotein B by the liver. J Inherit Metab Dis 1991, 14:915-922.
53. Venkatesan S., Cullen P., Pacy P.J., Halliday D., Scott J. Stable isotopes show a direct relation between VLDL apoB overproduction and serum triglyceride levels and indicate a metabolically and biochemically coherent basis for familial combined hyperlipidemia. Arterioscler Thromb 1993, 13:1110-1118.
54. Austin M.A., Krauss R.M. Genetic control of low-density-lipoprotein subclasses. Lancet 1986, 2:592-595.
55. Calabresi L., Donati D., Pazzucconi F., Sirtori C.R., Franceschini G. Omacor in familial combined hyperlipidemia: effects on lipids and low density lipoprotein subclasses. Atherosclerosis 2000, 148:387-396.
56. van der Vleuten G.M., Kluijtmans L.A., Hijmans A., Blom H.J., Stalenhoef A.F.H., de Graaf J. The Gln223Arg polymorphism in the leptin receptor is associated with familial combined hyperlipidemia. Int J Obes 2006, 30:892-898.
57. van der Vleuten G.M., Isaacs A., Hijmans A., van Dujin C.M., Stalenhoef A.F.H., de Graaf J. The involvement of upstream stimulatory factor 1 in Dutch patients with familial combined hyperlipidemia. J Lipid Res 2007, 48:193-200.
58. Ranjan N. Management of hyperlipidemias: an update. Indian J Dermatol Venereol Leprol 2009, 75:452-462.
59. Rozman D., Monostory K. Perspectives of the non-statin hypolipidemic agents. Pharmacol Ther 2010, 127:19-40.
60. Kontush A., Chapman M.J. Functionally defective high density lipoprotein:A new therapeutic target at the crossroads of dyslipidemia, inflammation, and atherosclerosis. Pharmacol Rev 2006, 58:342-374.
61. Jacobson T.A., Millar M., Schaefer E.J. Hypertriglyceridemia and cardiovascular risk reduction. Clin Therap 2007, 29:763-777.
62. Lin Y., Mousa S.S., Elshourbagy N., Mousa S.A. Current status and future directions in lipid management: emphasizing low density lipoproteins, high density lipoproteins, and triglycerides as targets for therapy. Vasc Health Risk Manag 2010, 6:73-85.
63. Willson T.M., Brown P.J., Sternbach D.D., Henke B.R. The PPARs: from orphan receptors to drug discovery. J Med Chem 2000, 43:527-550.
64. Pakala R., Kuchulakanti K., Rha S.W., Cheneau E., Baffour R., Waksman R. Peroxisome proliferator-activated receptor gamma: its role in metabolic syndrome. Cardiovasc Radiat Med 2004, 5:97-103.
65. Gross B.S., Fruchart J.C., Staels B. Peroxisome Proliferator-Activated Receptor β/δ: A novel target for the reduction of atherosclerosis. Drug Disc Today: Therap Strat 2005, 2:237-243.
66. Gervois P., Torra I.P., Fruchart J.C., Staels B. Regulation of lipid and lipoprotein metabolism by PPAR activators. Clin Chem Lab Med 2000, 38:3-11.
67. Chinetti G., Lestavel S., Bocher V., Remaley A.T., Neve B., Torra I.P., et al. PPAR-alpha and PPAR-gamma activators induce cholesterol removal from human macrophage foam cells through stimulation of the ABCA1 pathway. Nat Med 2001, 7:53-58.
68. Kasuga J., Yamasaki D., Araya Y., Nakagawa A., Makishima M., Doi T., et al. Design, synthesis, and evaluation of a novel series of a-substituted phenylpropanoic acid derivatives as human peroxisome proliferator-activated receptor (PPAR) α/δ dual agonists for the treatment of metabolic syndrome. Bioorg Med Chem 2006, 14:8405-8414.
69. Jeong H.W., Lee J.W., Kim W.S., Choe S.S., Shin H.J., Lee G.Y., et al. A nonthiazolidinedione peroxisome proliferator-activated receptor α/γ dual agonist CG301360 alleviates insulin resistance and lipid dysregulation in db/db mice. MolPharmacol 2010, 78:877-885.
70. Tall A.R. Plasma cholesteryl ester transfer protein. J Lipid Res 1993, 34:1255-1274.
71. Rano T.A., Sieber-McMaster E., Pelton P.D., Yang M., Demarest K.T., Kuo G. Design and synthesis of potent inhibitors of cholesteryl ester transfer protein (CETP) exploiting a 1,2,3,4-tetrahydroquinoline platform. Bioorg Med Chem Lett 2009, 19:2456-2460.
72. Champman J.M., Guerin M. CETP, a key player in atherogenic dyslipidemia of Type ii diabetes. Int Congr Ser 2004, 1262:503-506.
73. Gurfinkel R., Joy T.R. Anacetrapib: hope for CETP inhibitors?. Cardiovasc Therap 2011, 29:327-339.
74. Davidson M.H. Update on CETP inhibition. J Clin Lipidol 2010, 4:394-398.
75. Smith C.J., Ali A., Chen L., Hammond M.L., Anderson M.S., Chen Y., et al. 2-Arylbenzoxazoles as CETP inhibitors: substitution of the benzoxazole moiety. Bioorg Med Chem Lett 2010, 20:346-349.
76. Schmeck C., Gielen-Haertwig H., Vakalopoulos A., Bischoff H., Li V., Wirtz G., et al. Novel tetrahydrochinoline derived CETP inhibitors. Bioorg Med Chem Lett 2010, 20:1740-1743.
77. Vakalopoulos A., Schmeck C., Thutewohl M., Li V., Bischoff H., Lustig K., et al. Chromanol derivatives-A novel class of CETP inhibitors. Bioorg Med Chem Lett 2011, 21:488-491.
78. Sweis R.F., Hunt J.A., Kallashi F., Hammond M.L., Chen Y., Eveland S.S., et al. 2-(4-Carbonylphenyl) benzoxazole inhibitors of CETP: scaffold design and advancement in HDLc-raising efficacy. Bioorg Med Chem Lett 2011, 21:1890-1895.
79. Nutescu E.A., Shapiro N.L. Ezetimibe: a selective cholesterol absorption inhibitor. Pharmacotherapy 2003, 23:1463-1474.
80. Duntas L., Kolovou G. Options for the treatment of hyperlipidemia in type 2 diabetes mellitus and hypothyroidism: lowering the cardiovascular risk. Future Cardiol 2011, 7:137-144.
81. Athyros V.G., Tziomalos K., Karagiannis A., Mikhailidis D.P. Dyslipidaemia of obesity, metabolic syndrome and type 2 diabetes mellitus: the case for residual risk reduction after statin treatment. Open Cardiovasc Med J 2011, 5:24-34.
82. Jeu L., Cheng J.W. Pharmacology and therapeutics of ezetimibe (SCH 58235), a cholesterol-absorption inhibitor. Clin Ther 2003, 25:2352-2387.
83. Al-Shaer M.H., Choueiri N.E., Suleiman E.S. The pivotal role of cholesterol absorption inhibitors in the management of dyslipidemia. Lipids Health Dis 2004, 3:22.
84. Norum K.A., Lolljeqvist A., Helgerud P., Normann E.R., Selbekk A.M., Selbekk B. Esterification of cholesterol in humans small intestine: the importance of acyl-CoA:cholesterolacyltransferase. Eur J Clin Invest 1979, 9:55-62.
85. Insull W., Koren M., Davignon J., Sprecher D., Schrott H., Keilson L.M., et al. Efficacy and short-term safety of a new ACAT inhibitor, avasimibe, on lipids, lipoproteins, and apolipoproteins, in patients with combined hyperlipidemia. Atherosclerosis 2001, 157:137-144.
86. Asami Y., Kondo Y., Murakami S., Araki H., Tsuchida K., Higuchi S. The ACAT inhibitor HL-004 inhibits cholesterol absorption and lowers serum cholesterol in rats. Gen Pharmac 1998, 31:593-596.
87. Costet P. Molecular pathways and agents for lowering LDL-cholesterol in addition to statins. Pharmacol Ther 2010, 126:263-278.
88. Meuwese M.C., de Groot E., Duivenvoorden R., Trip M.D., Ose L., Maritz F.J., et al. ACAT Inhibition and progression of carotid atherosclerosis in patients with familial hypercholesterolemia. JAMA 2009, 301:1131-1139.
89. Lardizabal K.D., Mai J.T., Wagner N.W., Wyrick A., Voelker T., Hawkins D.J. DGAT2 is a new diacylglycerol acyltransferase gene family: purification, cloning, and expression in insect cells of two polypeptides from Mortierella ramanniana with diacylglycerol acyltransferase activity. J Biol Chem 2001, 276:38862-38869.
90. Zammit V.A., Buckett L.K., Turnbull A.V., Wure H., Proven A. Diacylglycerol acyltransferases: potential roles as pharmacological targets. Pharmacol Ther 2008, 118:295-302.
91. Jamil H., Gordon D.A., Eustice D.C., Brooks C.M., Dickson J.K., Chen Y., et al. An inhibitor of the microsomal triglyceride transfer protein inhibits apoB secretion from HepG2 cells. Proc Natl Acad Sci U S A 1996, 93:11991-11995.
92. Sulsky R., Robl J.A., Biller S.A., Harrity T.W., Wetterau J., Connolly F., et al. 5-Carboxamido-1,3,2-dioxaphosphorinanes, potent inhibitors of MTP. Bioorg Med Chem Lett 2004, 14:5067-5070.
93. Li J., Bertinato P., Cheng H., Cole B.M., Bronk B.S., Jaynes B.H., et al. Discovery of potent and orally active MTP inhibitors as potential anti-obesity agents. Bioorg Med Chem Lett 2006, 16:3039-3042.
94. Matsuda D., Tomoda H. DGAT inhibitors for obesity. Curr Opin Investig Drugs 2007, 10:836-841.
95. Rizzo M. Lomitapide, a microsomal triglyceride transfer protein inhibitor for the treatment of hypercholesterolemia. IDrugs 2010, 13:103-111.
96. Wetterau J.R., Gregg R.E., Harrity T.W., Arbeeny C., Cap M., Connolly F., et al. An MTP inhibitor that normalizes atherogenic lipoprotein levels in WHHL rabbits. Science 1998, 282:751-754.
97. Vu C.B., Milne J.C., Carney D.P., Song J., Choy W., Lambert P.D., et al. Discovery of benzothiazole derivatives as efficacious and enterocyte-specific MTP inhibitors. Bioorg Med Chem Lett 2009, 19:1416-1420.
98. Goldberg A.C. Novel therapies and new targets of treatment for familial hypercholesterolemia. J Clin Lipidol 2010, 4:350-356.
99. Kourounakis A.P., Matralis A.N., Nikitakis A. Design of more potent squalene synthase inhibitors with multiple activities. Bioorg Med Chem 2010, 18:7402-7412.
100. Hiyoshi H., Yanagimachi M., Ito M., Saeki T., Yoshida I., Okada T., et al. Squalene synthase inhibitors reduce plasma triglyceride through a low-density lipoprotein receptor-independent mechanism. Eur J Pharmacol 2001, 431:345-352.
101. Stein E.A. Other therapies for reducing low-density lipoprotein cholesterol: medications in development. Endocrinol Metab Clin North Am 2009, 38:99-119.
102. Davidson M.H. Novel nonstatin strategies to lower low-density lipoprotein cholesterol. Curr Atheroscler Rep 2009, 11:67-70.
103. Tavridou A., Manolopoulos V.G. Antioxidant properties of two novel 2-biphenylmorpholine compounds (EP2306 and EP2302) in vitro and in vivo. Eur J Pharmacol 2004, 505:213-221.
104. Tavridou A., Kaklamanis L., Megaritis G., Kourounakis A.P., Papalois A., Roukounas D., et al. Pharmacological characterization in vitro of EP2306 and EP2302, potent inhibitors of squalene synthase and lipid biosynthesis. Eur J Pharmacol 2006, 535:34-42.
105. Mason R.L., Hunt H.M., Hurxthal L.M. Blood cholesterol values in hyperthyroidism and hypothyroidism: their significance. N Engl J Med 1930, 203:1273-1278.
106. Morkin E., Ladenson P., Goldman S., Adamson C. Thyroid hormone analogs for treatment of hypercholesterolemia and heart failure: past, present and future prospects. J Mol Cell Cardiol 2004, 37:1137-1146.
107. Staels B., van Tol A., Chan L., Will H.M., Verhoeven G.A., Auwerx J. Alterations in thyroid status modulate apolipoprotein, hepatic triglyceride lipase, and low-density lipoprotein receptor in rats. Endocrinology 1990, 127:1144-1152.
108. Salter A.M., Hayashi R., Al-Seeni M., Brown N.F., Bruce J., Sorensen O., et al. Effects of hypothyroidism and high-fat feeding on mRNA concentrations for the low-density lipoprotein receptor and on acyl-CoA:cholesterol acyltransferase activities in rat liver. Biochem J 1991, 276:825-832.
109. Packard C.J., Shepard J., Lindsay G.M., Gaw A., Taskinen M.R. Thyroid replacement therapy and its influence on postheparin plasma lipases and apolipoprotein-b metabolism in hypothyroidism. J Clin Endocrinol Metab 1993, 76:1209-1216.
110. Baxter D.J., Webb P. Thyroid hormone mimetics: potential applications in atherosclerosis, obesity and type 2 diabetes. Nat Rev Drug Disc 2009, 8:308-320.
111. Ladenson P.W., Kristensen J.D., Ridgway E.C., Olsson A.G., Carlsson B., Klein I., et al. Use of the thyroid hormone analogue eprotirome in statin-treated dyslipidemia. N Engl J Med 2010, 362:906-916.
112. Korosec T., Acimovic J., Seliskar M., Kocjan D., Tacer K.F., Rozmanb D., Urleba U. Novel cholesterol biosynthesis inhibitors targeting human lanosterol 14a-demethylase (CYP51). Bioorg Med Chem 2008, 16:209-221.
113. Rowe A.H., Argmann C.A., Edwards J.Y., Sawyez C.G., Morand O.H., Hegele R.A., et al. Enhanced synthesis of the oxysterol 24(S), 25-epoxycholesterol in macrophages by inhibitors of 2, 3-oxidosqualene:lanosterol cyclase: A novel mechanism for the attenuation of foam cell formation. Circ Res 2003, 93:717-725.
114. Pikuleva I.A. Cholesterol-metabolizing cytochromes P450: implication for cholesterol lowering. Expert Opin Drug MetabToxicol 2008, 4:1403-1414.
115. Bjorkhem I., Reihnér E., Angelin B., Ewerth S., Akerlund J.E., Einarsson K. On the possible use of the serum level of 7 alpha-hydroxycholesterol as a marker for increased activity of the cholesterol 7 alpha-hydroxylase in humans. J Lipid Res 1987, 28:889-894.
116. Babiker A., Anderson O., Lund E., Xiu R.J., Deeb S., Reshef A., et al. Elimination of cholesterol in macrophages and endothelial cells by the sterol 27-hydroxylase mechanism. Comparison with high density lipoprotein-mediated reverse cholesterol transport. J Biol Chem 1997, 272:26253-26261.
117. Hardie D.G. Role of AMP-activated protein kinase in the metabolic syndrome and in heart disease. FEBS Lett 2008, 582:81-89.
118. Viollet B., Guigas B., Leclerc J., Hébrard S., Lantier L., Mounier R., et al. AMP-activated protein kinase in the regulation of hepatic energy metabolism: from physiology to therapeutic perspectives. Acta Physiol 2009, 196:81-98.
119. Henin N., Vincent M.F., Gruber H.E., van den Berghe G. Inhibition of fatty acid and cholesterol synthesis by stimulation of AMP-activated protein kinase. FASEB J 1995, 9:541-546.
120. Muoio D.M., Seefeld K., Witters L.A., Coleman R.A. AMP-activated kinase reciprocally regulates triacylglycerol synthesis and fatty acid oxidation in liver and muscle: evidence that sn-glycerol-3-phosphate acyltransferase is a novel target. Biochem J 1999, 338:783-791.
121. Lian Z., Li Y., Gao J., Qu K., Li J., Hao L., et al. A novel AMPK activator, WS070117, improves lipid metabolism discords in hamsters and HepG2 cells. Lipids Health Dis 2011, 10:1-8.
122. Durrington P.N., Bhatnager D., Mackness M.I., Morgan J., Julier K., Khan M.A., et al. An omega-3-polyunsaturated fatty acid concentrate administered for one year decreased triglycerides in simvastatin treated patients with coronary heart disease and persisting hypertriglyceridemia. Heart 2001, 85:544-548.