CETP inhibitors downregulate hepatic LDL receptor and PCSK9 expression invitro and invivo through a SREBP2 dependent mechanism

Atherosclerosis

Volumn 235, Issue 2, 2014, Pages 449-462

  Dong, Bin ^a   Singh, Amar Bahadur ^a   Fung, Chin ^a   Kan, Kelvin ^a   Liu, Jingwen ^a  

^a VA PALO ALTO HEALTH CARE SYSTEM   (United States)

Author keywords

CETP inhibitors; Hyperlipidemia; LDL receptor; PCSK9; SREBP2

Indexed keywords

ANACETRAPIB; CHOLESTEROL ESTER TRANSFER PROTEIN INHIBITOR; COMPLEMENTARY DNA; DALCETRAPIB; EVACETRAPIB; HIGH DENSITY LIPOPROTEIN CHOLESTEROL; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE INHIBITOR; LOW DENSITY LIPOPROTEIN CHOLESTEROL; LOW DENSITY LIPOPROTEIN RECEPTOR; PCSK9 PROTEIN; PROTEIN; RNA; ROSUVASTATIN; SMALL INTERFERING RNA; STEROL REGULATORY ELEMENT BINDING PROTEIN 2; TORCETRAPIB; UNCLASSIFIED DRUG; VERY LOW DENSITY LIPOPROTEIN CHOLESTEROL; CHOLESTEROL; CHOLESTEROL ESTER TRANSFER PROTEIN; HYPOCHOLESTEROLEMIC AGENT; LIPID; OXAZOLIDINONE DERIVATIVE; PCSK9 PROTEIN, HUMAN; SERINE PROTEINASE; THIOL DERIVATIVE;

ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; CELL VIABILITY ASSAY; CHOLESTEROL BLOOD LEVEL; CHOLESTEROL LIVER LEVEL; CONTROLLED STUDY; DRUG EFFECT; DRUG MECHANISM; HEPG2 CELL LINE; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; HUMAN; HUMAN CELL; HYPERCHOLESTEROLEMIA; HYPERLIPIDEMIA; IN VITRO STUDY; IN VIVO STUDY; LIPID DIET; LIVER CELL; MOUSE; NONHUMAN; PRIORITY JOURNAL; PROTEIN EXPRESSION; WESTERN BLOTTING; ANIMAL; ANTAGONISTS AND INHIBITORS; BIOSYNTHESIS; BLOOD; DOWN REGULATION; DYSLIPIDEMIA; MALE; METABOLISM; PHYSIOLOGY;

ANIMALS; ANTICHOLESTEREMIC AGENTS; CHOLESTEROL; CHOLESTEROL ESTER TRANSFER PROTEINS; DOWN-REGULATION; DYSLIPIDEMIAS; HEP G2 CELLS; HEPATOCYTES; HUMANS; LIPIDS; MALE; OXAZOLIDINONES; PROPROTEIN CONVERTASES; RECEPTORS, LDL; SERINE ENDOPEPTIDASES; STEROL REGULATORY ELEMENT BINDING PROTEIN 2; SULFHYDRYL COMPOUNDS;

EID: 84920513669     PISSN: 00219150     EISSN: 18791484     Source Type: Journal    
DOI: 10.1016/j.atherosclerosis.2014.05.931     Document Type: Article

References (49)

1. Grundy S.M., Cleeman J.I., Merz C.N., Brewer H.B., Clark L.T., Hunninghake D.B., et al. Implications of recent clinical trials for the national cholesterol education program adult treatment panel III guidelines. JAm Coll Cardiol 2004, 44:720-732.
2. Spady D.K. Hepatic clearance of plasma low density lipoproteins. Semin Liver Dis 1996, 12:373-385.
3. Brown M.S., Goldstein J.L. Areceptor-mediated pathway for cholesterol homeostasis. Science 1986, 232:34-47.
4. Goldstein J.L., Brown M.S. Regulation of the mevalonate pathway. Nature 1990, 343:425-430.
5. Grundy S.M. Statin trials and goals of cholesterol-lowering therapy. Circulation 1998, 97:1436-1439.
6. Clark R.W. Raising high-density lipoprotein with cholesteryl ester transfer protein inhibitors. Curr Opin Pharmacol 2006, 6:162-168.
7. Clark R.W., Ruggeri R.B., Cunningham D., Bamberger M.J. Description of the torcetrapib series of cholesteryl ester transfer protein inhibitors, including mechanism of action. JLipid Res 2006, 47:537-552.
8. Chapman M.J., Le G.W., Guerin M., Kontush A. Cholesteryl ester transfer protein: at the heart of the action of lipid-modulating therapy with statins, fibrates, niacin, and cholesteryl ester transfer protein inhibitors. Eur Heart J 2010, 31:149-164.
9. Miyares M.A., Davis K. Patient considerations and clinical impact of cholesteryl ester transfer protein inhibitors in the management of dyslipidemia: focus on anacetrapib. Vasc Health Risk Manag 2012, 8:483-493.
10. Ballantyne C.M., Miller M., Niesor E.J., Burgess T., Kallend D., Stein E.A. Effect of dalcetrapib plus pravastatin on lipoprotein metabolism and high-density lipoprotein composition and function in dyslipidemic patients: results of a phase IIb dose-ranging study. Am Heart J 2012, 163:515-521.
11. de Grooth G.J., Kuivenhoven J.A., Stalenhoef A.F., de G.J., Zwinderman A.H., Posma J.L., et al. Efficacy and safety of a novel cholesteryl ester transfer protein inhibitor, JTT-705, in humans: a randomized phase II dose-response study. Circulation 2002, 105:2159-2165.
12. Stroes E.S., Kastelein J.J., Benardeau A., Kuhlmann O., Blum D., Campos L.A., et al. Dalcetrapib: no off-target toxicity on blood pressure or on genes related to the renin-angiotensin-aldosterone system in rats. Br J Pharmacol 2009, 158:1763-1770.
13. Stein E.A., Stroes E.S., Steiner G., Buckley B.M., Capponi A.M., Burgess T., et al. Safety and tolerability of dalcetrapib. Am J Cardiol 2009, 104:82-91.
14. Gutstein D.E., Krishna R., Johns D., Surks H.K., Dansky H.M., Shah S., et al. Anacetrapib, a novel CETP inhibitor: pursuing a new approach to cardiovascular risk reduction. Clin Pharmacol Ther 2012, 91:109-122.
15. Krishna R., Bergman A.J., Green M., Dockendorf M.F., Wagner J.A., Dykstra K. Model-based development of anacetrapib, a novel cholesteryl ester transfer protein inhibitor. AAPS J 2011, 13:179-190.
16. Krishna R., Bergman A.J., Jin B., Fallon M., Cote J., Van H.P., et al. Multiple-dose pharmacodynamics and pharmacokinetics of anacetrapib, a potent cholesteryl ester transfer protein (CETP) inhibitor, in healthy subjects. Clin Pharmacol Ther 2008, 84:679-683.
17. Krishna R., Anderson M.S., Bergman A.J., Jin B., Fallon M., Cote J., 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, 370:1907-1914.
18. Cao G., Beyer T.P., Zhang Y., Schmidt R.J., Chen Y.Q., Cockerham S.L., et al. Evacetrapib is a novel, potent, and selective inhibitor of cholesteryl ester transfer protein that elevates HDL cholesterol without inducing aldosterone or increasing blood pressure. JLipid Res 2011, 52:2169-2176.
19. Barter P.J., Caulfield M., Eriksson M., Grundy S.M., Kastelein J.J., Komajda M., et al. Effects of torcetrapib in patients at high risk for coronary events. NEngl J Med 2007, 357:2109-2122.
20. Schwartz G.G., Olsson A.G., Abt M., Ballantyne C.M., Barter P.J., Brumm J., et al. Effects of dalcetrapib in patients with a recent acute coronary syndrome. NEngl J Med 2012, 29(367):2089-2099.
21. Schwartz G.G., Olsson A.G., Ballantyne C.M., Barter P.J., Holme I.M., Kallend D., et al. Rationale and design of the dal-OUTCOMES trial: efficacy and safety of dalcetrapib in patients with recent acute coronary syndrome. Am Heart J 2009, 158:896-901.
22. Bloomfield D., Carlson G.L., Sapre A., Tribble D., McKenney J.M., Littlejohn T.W., et al. Efficacy and safety of the cholesteryl ester transfer protein inhibitor anacetrapib as monotherapy and coadministered with atorvastatin in dyslipidemic patients. Am Heart J 2009, 157:352-360.
23. Davidson M., Liu S.X., Barter P., Brinton E.A., Cannon C.P., Gotto A.M., et al. Measurement of LDL-C after treatment with the CETP inhibitor anacetrapib. JLipid Res 2013, 54:467-472.
24. Castro-Perez J., Briand F., Gagen K., Wang S.P., Chen Y., McLaren D.G., et al. Anacetrapib promotes reverse cholesterol transport and bulk cholesterol excretion in Syrian golden hamsters. JLipid Res 2011, 52:1965-1973.
25. Wang S.P., Daniels E., Chen Y., Castro-Perez J., Zhou H., Akinsanya K.O., et al. Invivo effects of anacetrapib on prebeta HDL: improvement in HDL remodeling without effects on cholesterol absorption. JLipid Res 2013, 54:2858-2865.
26. Briand F., Thieblemont Q., Muzotte E., Sulpice T. Upregulating reverse cholesterol transport with cholesteryl ester transfer protein inhibition requires combination with the LDL-lowering drug berberine in dyslipidemic hamsters. Arterioscler Thromb Vasc Biol 2013, 33:13-23.
27. Niesor E.J., Magg C., Ogawa N., Okamoto H., von der M.E., Matile H., et al. Modulating cholesteryl ester transfer protein activity maintains efficient pre-beta-HDL formation and increases reverse cholesterol transport. JLipid Res 2010, 51:3443-3454.
28. Bell T.A., Graham M.J., Lee R.G., Mullick A.E., Fu W., Norris D., et al. Antisense oligonucleotide inhibition of cholesteryl ester transfer protein enhances RCT in hyperlipidemic, CETP transgenic, LDLr-/- mice. JLipid Res 2013, 54:2647-2657.
29. Seidah N.G. PCSK9 as a therapeutic target of dyslipidemia. Expert Opin Ther Targets 2009, 13:19-28.
30. Lambert G., Sjouke B., Choque B., Kastelein J.J., Hovingh G.K. The PCSK9 decade. JLipid Res 2012, 53:2515-2524.
31. McKenney J.M., Koren M.J., Kereiakes D.J., Hanotin C., Ferrand A.C., Stein E.A. Safety and efficacy of a monoclonal antibody to proprotein convertase subtilisin/kexin type 9 serine protease, SAR236553/REGN727, in patients with primary hypercholesterolemia receiving ongoing stable atorvastatin therapy. JAm Coll Cardiol 2012, 59:2344-2353.
32. Graham M.J., Lemonidis K.M., Whipple C.P., Subramaniam A., Monia B.P., Crooke S.T., et al. Antisense inhibition of proprotein convertase subtilisin/kexin type 9 reduces serum LDL in hyperlipidemic mice. JLipid Res 2007, 48:763-767.
33. Frank-Kamenetsky M., Grefhouse A., Anderson N.N., Racie T.S., Bramlage B., Akinc A., et al. Therapeutic RNAi targeting PCSK9 acutely lowers plasma cholesterol in rodents and LDL cholesterol in nonhuman primates. Proc Natl Acad Sci USA 2008, 105:11915-11920.
34. Shibata H., Murakami K., Murakami T., Miyosawa K., Iwashita M., Yamazaki H., et al. Inhibitor K-312 with PCSK9 inhibitory property, exerts strong reduction of LDL-c and anti-atherosclerotic effects. Circulation 2012, 126:A11879-a11880.
35. Miyosawa K., Watanabe Y., Murakami T., Desai D., Jiro Matsumoto J., Tanabe S., et al. Anovel CETP inhibitor, K-312, suppresses PCSK9 expression through the modulation of its promoter activity. Circulation 2012, 126:A13436-A13437.
36. Horton J.D., Shah N.A., Warrington J.A., Anderson N.N., Park S.W., Brown M.S., 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, 100:12027-12032.
37. Dubuc G., Chamberland A., Wassef H., Davignon J., Seidah N.G., Bernier L., 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, 24:1454-1459.
38. Jeong H.J., Lee H.-S., Kim K.-S., Kim Y.-K., Yoon D., Park S.W. Sterol-dependent regulation of proprotein convertase subtilisin/kexin type 9 expression by sterol-regulatory element binding protein-2. JLipid Res 2008, 49:399-409.
39. Bengoechea-Alonso M.T., Ericsson J. SREBP in signal transduction: cholesterol metabolism and beyond. Curr Opin Cell Biol 2007, 19:215-222.
40. Costet P., Cariou B., Lambert G., Lalanne F., Lardeux B., Jarnoux A.-L., et al. Hepatic PCSK9 expression is regulated by nutritional status via insulin and sterol regulatory element-binding protein 1c. JBiol Chem 2006, 281:6211-6218.
41. Li H., Dong B., Park S.W., Lee H.-S., Chen W., Liu J. Hepatocyte nuclear factor 1α plays a critical role in PCSK9 gene transcription and regulation by the natural hypocholesterolemic compound berberine. JBiol Chem 2009, 284:28885-28895.
42. Liu H., Fenollar-Ferrer C., Cao A., Anselmi C., Carloni P., Liu J. Molecular dissection of human oncostatin M-mediated signal transductions through site-directed mutagenesis. Int J Mol Med 2009, 23:161-172.
43. Liu J., Streiff R., Zhang Y.L., Vestal R.E., Spence M.J., Briggs M.R. Novel mechanism of transcriptional activation of hepatic LDL receptor by oncostatin M. JLipid Res 1997, 38:2035-2048.
44. Dong B., Kan C.F., Singh A.B., Liu J. High-fructose diet downregulates long-chain acyl-CoA synthetase 3 expression in liver of hamsters via impairing LXR/RXR signaling pathway. JLipid Res 2013, 54:1241-1254.
45. Dong B., Wu M., Li H., Kraemer F.B., Adeli K., Seidah N.G., et al. Strong induction of PCSK9 gene expression through HNF1α and SREBP2: mechanism for the resistance to LDL-cholesterol lowering effect of statins in dyslipidemic hamsters. JLipid Res 2010, 51:1486-1495.
46. Reagan-Shaw S., Nihal M., Ahmad S. Dose translation from animal to human studies revisited. FASEB J 2007, 22:659-661.
47. Miyares M.A. ANA and DAL: two novel cholesteryl ester transfer protein inhibitors. Ann Pharmacother 2011, 45:84-94.
48. Brown M.S., Goldstein J.L. Aproteolytic pathway that controls the cholesterol content of membranes, cells, and blood. Proc Natl Acad Sci USA 1999, 96:11041-11048.
49. Yang C., McDonald J.G., Patel A., Zhang Y., Umetani M., Xu F., et al. Sterol intermediates from cholesterol biosynthetic pathway as liver X receptor ligands. JBiol Chem 2006, 281:27816-27826.