RVX-208. A Small Molecule That Increases Apolipoprotein A-I and High-Density Lipoprotein Cholesterol In Vitro and In Vivo

Journal of the American College of Cardiology

Volumn 55, Issue 23, 2010, Pages 2580-2589

  Bailey, Dana ^a   Jahagirdar, Ravi ^b   Gordon, Allan ^b   Hafiane, Anouar ^a   Campbell, Steven ^a   Chatur, Safia ^a   Wagner, Gregory S ^b   Hansen, Henrik C ^b   Chiacchia, Fabrizio S ^b   Johansson, Jan ^b   Krimbou, Larbi ^a   Wong, Norman C W ^b   Genest, Jacques ^a  

^a ROYAL VICTORIA HOSPITAL   (Canada)

^b Resverlogix Corp   (Canada)

Author keywords

apoA I; atherosclerosis; HDL based therapy; reverse cholesterol transport

Indexed keywords

ABC TRANSPORTER A1; ABC TRANSPORTER G1; ANTILIPEMIC AGENT; APOLIPOPROTEIN A1; CHOLESTEROL ESTER TRANSFER PROTEIN; HIGH DENSITY LIPOPROTEIN CHOLESTEROL; PLACEBO; RVX 208; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; ATHEROSCLEROTIC CARDIOVASCULAR DISEASE; CHOLESTEROL BLOOD LEVEL; CHOLESTEROL ESTERIFICATION; CLINICAL TRIAL; CONTROLLED CLINICAL TRIAL; CONTROLLED STUDY; DRUG ABSORPTION; DRUG BIOAVAILABILITY; DRUG BLOOD LEVEL; DRUG CLEARANCE; DRUG DISTRIBUTION; DRUG EFFICACY; DRUG HALF LIFE; DRUG SAFETY; DRUG TOLERABILITY; GENE EXPRESSION; HUMAN; HUMAN CELL; HUMAN EXPERIMENT; IN VITRO STUDY; IN VIVO STUDY; LIPOPROTEIN BLOOD LEVEL; MALE; NONHUMAN; NORMAL HUMAN; PRIORITY JOURNAL; PROTEIN FUNCTION; PROTEIN SYNTHESIS; SINGLE DRUG DOSE;

ANIMALS; APOLIPOPROTEIN A-I; CELLS, CULTURED; CERCOPITHECUS AETHIOPS; CHOLESTEROL, HDL; CRICETINAE; DISEASE MODELS, ANIMAL; DOSE-RESPONSE RELATIONSHIP, DRUG; DRUG ADMINISTRATION SCHEDULE; FEMALE; FOLLOW-UP STUDIES; HEP G2 CELLS; HUMANS; MACACA FASCICULARIS; MALE; MOLECULAR WEIGHT; PROBABILITY; QUINAZOLINES; RANDOM ALLOCATION; RISK ASSESSMENT;

EID: 77952713824     PISSN: 07351097     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.jacc.2010.02.035     Document Type: Article

References (34)

1. Duffy D., and Rader D.J. Emerging therapies targeting high-density lipoprotein metabolism and reverse cholesterol transport. Circulation 113 (2006) 1140-1150
2. Tall A.R. Plasma high density lipoproteins. Metabolism and relationship to atherogenesis. J Clin Invest 86 (1990) 379-384
3. Brewer H.B. High-density lipoproteins: a new potential therapeutic target for the prevention of cardiovascular disease. Arterioscler Thromb Vasc Biol 24 (2004) 387-391
4. Nissen S.E., Tsunoda T., Tuzcu E.M., et al. Effect of recombinant ApoA-I Milano on coronary atherosclerosis in patients with acute coronary syndromes: a randomized controlled trial. JAMA 290 (2003) 2292-2300
5. Krimbou L., Marcil M., and Genest J. New insights into the biogenesis of human high-density lipoproteins. Curr Opin Lipidol 17 (2006) 258-267
6. Cockerill G.W., Saklatvala J., Ridley S.H., et al. High-density lipoproteins differentially modulate cytokine-induced expression of E-selectin and cyclooxygenase-2. Arterioscler Thromb Vasc Biol 19 (1999) 910-917
7. Navab M., Ananthramaiah G.M., Reddy S.T., et al. The oxidation hypothesis of atherogenesis: the role of oxidized phospholipids and HDL. J Lipid Res 45 (2004) 993-1007
8. Griffin J.H., Kojima K., Banka C.L., Curtiss L.K., and Fernandez J.A. High-density lipoprotein enhancement of anticoagulant activities of plasma protein S and activated protein C. J Clin Invest 103 (1999) 219-227
9. Krimbou L., Tremblay M., Davignon J., and Cohn J.S. Characterization of human plasma apolipoprotein E-containing lipoproteins in the high density lipoprotein size range: focus on pre-beta1-LpE, pre-beta2-LpE, and alpha-LpE. J Lipid Res 38 (1997) 35-48
10. Vaughan A.M., and Oram J.F. ABCG1 redistributes cell cholesterol to domains removable by high density lipoprotein but not by lipid-depleted apolipoproteins. J Biol Chem 280 (2005) 30150-30157
11. Chisholm J.W., Gebre A.K., and Parks J.S. Characterization of C-terminal histidine-tagged human recombinant lecithin:cholesterol acyltransferase. J Lipid Res 40 (1999) 1512-1519
12. Krimbou L., Tremblay M., Jacques H., Davignon J., and Cohn J.S. In vitro factors affecting the concentration of gamma-LpE (gamma-LpE) in human plasma. J Lipid Res 39 (1998) 861-872
13. Krimbou L., Hajj H.H., Blain S., et al. Biogenesis and speciation of nascent apoA-I-containing particles in various cell lines. J Lipid Res 46 (2005) 1668-1677
14. Kieft K.A., Bocan T.M., and Krause B.R. Rapid on-line determination of cholesterol: distribution among plasma lipoproteins after high-performance gel filtration chromatography. J Lipid Res 32 (1991) 859-866
15. Lipinski C.A., Lombardo F., Dominy B.W., and Feeney P.J. Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Advanced Drug Delivery Reviews 46 (2001) 3-26
16. Veber D.F., Johnson S.R., Cheng H.Y., Smith B.R., Ward K.W., and Kopple K.D. Molecular properties that influence the oral bioavailability of drug candidates. J Med Chem 45 (2002) 2615-2623
17. Ward K.W., Coon D.J., Magiera D., Bhadresa S., Nisbett E., and Lawrence M.S. Exploration of the African Green Monkey as a preclinical pharmacokinetic model: intravenous pharmacokinetic parameters. Drug Metab Dispos 36 (2008) 715-720
18. Brousseau M.E., Diffenderfer M.R., Millar J.S., et al. Effects of cholesteryl ester transfer protein inhibition on high-density lipoprotein subspecies, apolipoprotein A-I metabolism, and fecal sterol excretion. Arterioscler Thromb Vasc Biol 25 (2005) 1057-1064
19. Basso F., Freeman L., Knapper C., et al. Role of the hepatic ABCA1 transporter in modulating intrahepatic cholesterol and plasma HDL cholesterol concentrations. J Lipid Res 44 (2003) 296-302
20. Timmins J.M., Lee J.Y., Boudyguina E., et al. Targeted inactivation of hepatic Abca1 causes profound hypoalphalipoproteinemia and kidney hypercatabolism of apoA-I. J Clin Invest 115 (2005) 1333-1342
21. Schaefer E.J., Zech L.A., Jenkins L.L., et al. Human apolipoprotein A-I and A-II metabolism. J Lipid Res 23 (1982) 850-862
22. Parks J.S., and Rudel L.L. Different kinetic fates of apolipoproteins A-I and A-II from lymph chylomicra of nonhuman primates. Effect of saturated versus polyunsaturated dietary fat. J Lipid Res 23 (1982) 410-421
23. Barter P.J. Hugh Sinclair lecture: the regulation and remodelling of HDL by plasma factors. Atheroscler Suppl 3 (2002) 39-47
24. Dobiasova M., Stribrna J., Sparks D.L., Pritchard P.H., and Frohlich J.J. Cholesterol esterification rates in very low density lipoprotein- and low density lipoprotein-depleted plasma. Relation to high density lipoprotein subspecies, sex, hyperlipidemia, and coronary artery disease. Arterioscler Thromb Vasc Biol 11 (1991) 64-70
25. Sethi A.A., Sampson M., Warnick R., Nordestgaard B.G., Tybjaerg-Hansen A., and Remaley A.T. Pre-beta HDL and lecithin:cholesterol acyltransferase levels are strong positive diagnostic risk markers for ischemic heart disease in subjects with both high and low HDL-C levels in the Copenhagen City Heart Study (abstr). Circulation 118 (2008) S370
26. Amir F.A., Sandra H.M., Sammy C., Mancini G.B.J., John S.H., and Jiri J.F. Lecithin: cholesterol acyltransferase (LCAT) deficiency and risk of vascular disease: 25 year follow-up. Atherosclerosis 177 (2004) 361-366
27. Gardner C.D., Fortmann S.P., and Krauss R.M. Association of small low-density lipoprotein particles with the incidence of coronary artery disease in men and women. JAMA 276 (1996) 875-881
28. Schaefer E.J., McNamara J.R., Tayler T., et al. Effects of atorvastatin on fasting and postprandial lipoprotein subclasses in coronary heart disease patients versus control subjects. Am J Cardiol 90 (2002) 689-696
29. Johansson J., Carlson L., Landou C., and Hamsten A. High density lipoproteins and coronary atherosclerosis. A strong inverse relation with the largest particles is confined to normotriglyceridemic patients. Arterioscler Thromb Vasc Biol 11 (1991) 174-182
30. Barter P., Gotto A.M., LaRosa J.C., et al. HDL cholesterol, very low levels of LDL cholesterol, and cardiovascular events. N Engl J Med 357 (2007) 1301-1310
31. Wang X., Collins H.L., Ranalletta M., et al. Macrophage ABCA1 and ABCG1, but not SR-BI, promote macrophage reverse cholesterol transport in vivo. J Clin Invest 117 (2007) 2216-2224
32. Hassan H.H., Blain S., Boucher B., Denis M., Krimbou L., and Genest J. Structural modification of plasma HDL by phospholipids promotes efficient ABCA1-mediated cholesterol release. J Lipid Res 46 (2005) 1457-1465
33. Kennedy M.A., Barrera G.C., Nakamura K., et al. ABCG1 has a critical role in mediating cholesterol efflux to HDL and preventing cellular lipid accumulation. Cell Metab 1 (2005) 121-131
34. Jian B., Llera-Moya M., Ji Y., et al. Scavenger receptor class B type I as a mediator of cellular cholesterol efflux to lipoproteins and phospholipid acceptors. J Biol Chem 273 (1998) 5599-5606