Varespladib: Targeting the inflammatory face of atherosclerosis

European Heart Journal

Volumn 32, Issue 8, 2011, Pages 923-926

  Arsenault, Benoit J ^a   Boekholdt, S Matthijs ^a   Kastelein, John J P ^a  

^a UNIVERSITY OF AMSTERDAM   (Netherlands)

Author keywords

[No Author keywords available]

Indexed keywords

APOLIPOPROTEIN B; ATORVASTATIN; C REACTIVE PROTEIN; DARAPLADIB; HIGH DENSITY LIPOPROTEIN; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE INHIBITOR; ICOSANOID; LEUKOTRIENE; LOW DENSITY LIPOPROTEIN CHOLESTEROL; PLACEBO; PROSTAGLANDIN; PROTEOGLYCAN; SECRETORY PHOSPHOLIPASE A2; THROMBOCYTE ACTIVATING FACTOR; TRIACYLGLYCEROL; VARESPLADIB;

ATHEROSCLEROSIS; CHOLESTEROL BLOOD LEVEL; DRUG EFFICACY; HUMAN; ISCHEMIC HEART DISEASE; LIPID METABOLISM; LIPOPROTEIN BLOOD LEVEL; NUCLEAR MAGNETIC RESONANCE SPECTROSCOPY; PHASE 3 CLINICAL TRIAL (TOPIC); PRIORITY JOURNAL; PROTEIN BLOOD LEVEL; RANDOMIZED CONTROLLED TRIAL (TOPIC); REVIEW; SINGLE NUCLEOTIDE POLYMORPHISM;

ACETATES; CORONARY DISEASE; FEMALE; HUMANS; HYDROXYMETHYLGLUTARYL-COA REDUCTASE INHIBITORS; INDOLES; MALE; PHOSPHOLIPASES A2, SECRETORY;

EID: 79954496787     PISSN: 0195668X     EISSN: 15229645     Source Type: Journal    
DOI: 10.1093/eurheartj/ehq385     Document Type: Review

References (21)

1. Libby P. Inflammation in atherosclerosis. Nature 2002;420:868-874. (Pubitemid 36019640)
2. Stafforini DM, Prescott SM, McIntyre TM. Human plasma platelet-activating factor acetylhydrolase. Purification and properties. J Biol Chem 1987;262:4223-4230. (Pubitemid 17102640)
3. Hurt-Camejo E, Camejo G, Peilot H, Oorni K, Kovanen P. Phospholipase A(2) in vascular disease. Circ Res 2001;89:298-304.
4. Teslovich TM, Musunuru K, Smith AV, Edmondson AC, Stylianou IM, Koseki M, Pirruccello JP, Ripatti S, Chasman DI, Willer CJ, Johansen CT, Fouchier SW, Isaacs A, Peloso GM, Barbalic M, Ricketts SL, Bis JC, Aulchenko YS, Thorleifsson G, Feitosa MF, Chambers J, Orho-Melander M, Melander O, Johnson T, Li X, Guo X, Li M, Shin Cho Y, Jin Go M, Jin Kim Y, Lee JY, Park T, Kim K, Sim X, Twee-Hee Ong R, Croteau-Chonka DC, Lange LA, Smith JD, Song K, Hua Zhao J, Yuan X, Luan J, Lamina C, Ziegler A, Zhang W, Zee RY, Wright AF, Witteman JC, Wilson JF, Willemsen G, Wichmann HE, Whitfield JB, Waterworth DM, Wareham NJ, Waeber G, Vollenweider P, Voight BF, Vitart V, Uitterlinden AG, Uda M, Tuomilehto J, Thompson JR, Tanaka T, Surakka I, Stringham HM, Spector TD, Soranzo N, Smit JH, Sinisalo J, Silander K, Sijbrands EJ, Scuteri A, Scott J, Schlessinger D, Sanna S, Salomaa V, Saharinen J, Sabatti C, Ruokonen A, Rudan I, Rose LM, Roberts R, Rieder M, Psaty BM, Pramstaller PP, Pichler I, Perola M, Penninx BW, Pedersen NL, Pattaro C, Parker AN, Pare G, Oostra BA, O'Donnell CJ, Nieminen MS, Nickerson DA, Montgomery GW, Meitinger T, McPherson R, McCarthy MI, McArdle W, Masson D, Martin NG, Marroni F, Mangino M, Magnusson PK, Lucas G, Luben R, loos RJ, Lokki ML, Lettre G, Langenberg C, Launer LJ, Lakatta EG, Laaksonen R, Kyvik KO, Kronenberg F, Konig IR, Khaw KT, Kaprio J, Kaplan LM, Johansson A, Jarvelin MR, Cecile JW Janssens A, Ingelsson E, Igl W, Hovingh GK, Hottenga JJ, Hofman A, Hicks AA, Hengstenberg C, Heid IM, Hayward C, Havulinna AS, Hastie ND, Harris TB, Haritunians T, Hall AS, Gyllensten U, Guiducci C, Groop LC, Gonzalez E, Gieger C, Freimer NB, Ferrucci L, Erdmann J, Elliott P, Ejebe KG, Doring A, Dominiczak AF, Demissie S, Deloukas P, de Geus EJ, de Faire U, Crawford G, Collins FS, Chen YD, Caulfield MJ, Campbell H, Burtt NP, Bonnycastle LL, Boomsma DI, Boekholdt SM, Bergman RN, Barroso I, Bandinelli S, Ballantyne CM, Assimes TL, Quertermous T, Altshuler D, Seielstad M, Wong TY, Tai ES, Feranil AB, Kuzawa CW, Adair LS, Taylor HA Jr, Borecki IB, Gabriel SB, Wilson JG, Holm H, Thorsteindottir U, Gudnason V, Krauss RM, Mohlke KL, Ordovas JM, Munroe PB, Kooner JS, Tall AR, Hegele RA, Kastelein JJ, Schadt EE, Rotter JI, Boerwinkle E, Schrachan DP, Mooser V, Stefansson K, Reilly MP, Samani NJ, Schunkert H, Cupples LA, Sandhu MS, Ridker PM, Rader DJ, van Duijn CM, Peltonen L, Abecasis GR, Boehnke M, Kathiresan S. Biological, clinical and population relevance of 95 loci for blood lipids. Nature 2010;466:707-713.
5. Thompson A, Gao P, Orfei L, Watson S, Di Angelantonio E, Kaptoge S, Ballantyne C, Cannon CP, Criqui M, Cushman M, Hofman A, Packard C, Thompson SG, Collins R, Danesh J. Lipoprotein-associated phospholipase A(2) and risk of coronary disease, stroke, and mortality: collaborative analysis of 32 prospective studies. Lancet 2010;375:1536-1544.
6. Casas JP, Ninio E, Panayiotou A, Palmen J, Cooper JA, Ricketts SL, Sofat R, Nicolaides AN, Corsetti JP, Fowkes FG, Tzoulaki I, Kumari M, Brunner EJ, Kivimaki M, Marmot MG, Hoffmann MM, Winkler K, Marz W, Ye S, Stirnadel HA, Boekholdt SM, Khaw KT, Humphries SE, Sandhu MS, Hingorani AD, Talmud PJ. PLA2G7 genotype, lipoprotein-associated phospholipase A2 activity, and coronary heart disease risk in 10 494 cases and 15 624 controls of European Ancestry. Circulation 2010;121:2284-2293.
7. Serruys PW, Garcia-Garcia HM, Buszman P, Erne P, Verheye S, Aschermann M, Duckers H, Bleie O, Dudek D, Botker HE, von Birgelen C, D'Amico D, Hutchinson T, Zambanini A, Mastik F, van Es GA, van der Steen AF, Vince DG, Ganz P, Hamm CW, Wijns W, Zalewski A. Effects of the direct lipoprotein-associated phospholipase A(2) inhibitor darapladib on human coronary atherosclerotic plaque. Circulation 2008;118:1172-1182.
8. www.clinicaltrials.gov. Accessed 27 August 2010.
9. Nijmeijer R, Meuwissen M, Krijnen PA, van der Wal A, Piek JJ, Visser CA, Hack CE, Niessen HW. Secretory type II phospholipase A2 in culprit coronary lesions is associated with myocardial infarction. Eur J Clin Invest 2008;38:205-210. (Pubitemid 351389139)
10. Kugiyama K, Ota Y, Takazoe K, Moriyama Y, Kawano H, Miyao Y, Sakamoto T, Soejima H, Ogawa H, Doi H, Sugiyama S, Yasue H. Circulating levels of secretory type II phospholipase A(2) predict coronary events in patients with coronary artery disease. Circulation 1999;100:1280-1284. (Pubitemid 29440119)
11. Boekholdt SM, Keller TT, Wareham NJ, Luben R, Bingham SA, Day NE, Sandhu MS, Jukema JW, Kastelein JJ, Hack CE, Khaw KT. Serum levels of type II secretory phospholipase A2 and the risk of future coronary artery disease in apparently healthy men and women: the EPIC-Norfolk Prospective Population Study. Arterioscler Thromb Vasc Biol 2005;25:839-846. (Pubitemid 40463879)
12. Mallat Z, Benessiano J, Simon T, Ederhy S, Sebella-Arguelles C, Cohen A, Huart V, Wareham NJ, Luben R, Khaw KT, Tedgui A, Boekholdt SM. Circulating secretory phospholipase A2 activity and risk of incident coronary events in healthy men and women: the EPIC-Norfolk study. Arterioscler Thromb Vasc Biol 2007;27:1177-1183. (Pubitemid 46641976)
13. Divchev D, Grothusen C, Luchtefeld M, Thoenes M, Onono F, Koch R, Drexler H, Schieffer B. Impact of a combined treatment of angiotensin II type 1 receptor blockade and 3-hydroxy-3-methyl-glutaryl-CoA-reductase inhibition on secretory phospholipase A2-type IIA and low density lipoprotein oxidation in patients with coronary artery disease. Eur Heart J 2008;29:1956-1965.
14. Shaposhnik Z, Wang X, Trias J, Fraser H, Lusis AJ. The synergistic inhibition of atherogenesis in apoE-/- mice between pravastatin and the sPLA2 inhibitor varespladib (A-002). J Lipid Res 2009;50:623-629.
15. Leite JO, Vaishnav U, Puglisi M, Fraser H, Trias J, Fernandez ML. A-002 (Varespladib), a phospholipase A2 inhibitor, reduces atherosclerosis in guinea pigs. BMC Cardiovasc Disord 2009;9:7.
16. Rosenson RS, Hislop C, McConnell D, Elliott M, Stasiv Y, Wang N, Waters DD. Effects of 1-H-indole-3-glyoxamide (A-002) on concentration of secretory phospholipase A2 (PLASMA study): a phase II double-blind, randomised, placebocontrolled trial. Lancet 2009;373:649-658.
17. Rosenson RS, Elliott M, Stasiv Y, Hislop C, for the PLASMA II Investigators. Randomized trial of an inhibitor of secretory phospholipase A2 on atherogenic lipoprotein subclasses in statin-treated patients with coronary heart disease. Eur Heart J 2011;32:999-1005. First published on 16 November 2010. doi:10.1093/ eurheartj/ehq374.
18. Rosenson RS, Hislop C, Elliott M, Stasiv Y, Goulder M, Waters D. Effects of varespladib methyl on biomarkers and major cardiovascular events in acute coronary syndrome patients. J Am Coll Cardiol 2010;56:1079-1088.
19. Kastelein JJ, Akdim F, Stroes ES, Zwinderman AH, Bots ML, Stalenhoef AF, Visseren FL, Sijbrands EJ, Trip MD, Stein EA, Gaudet D, Duivenvoorden R, Veltri EP, Marais AD, de Groot E. Simvastatin with or without ezetimibe in familial hypercholesterolemia. N Engl J Med 2008;358:1431-1443. (Pubitemid 351482735)
20. Arsenault BJ, Lemieux I, Després JP,Wareham NJ, Luben R, Kastelein JJ, Khaw KT, Boekholdt MS. Cholesterol levels in small LDL particles predict the risk of coronary heart disease in the EPIC-Norfolk prospective population study. Eur Heart J 2007;28:2770-2777. (Pubitemid 350135531)
21. Tardif JC, McMurray JJ, Klug E, Small R, Schumi J, Choi J, Cooper J, Scott R, Lewis EF, L'Allier PL, Pfeffer MA. Effects of succinobucol (AGI-1067) after an acute coronary syndrome: a randomised, double-blind, placebo-controlled trial. Lancet 2008;371:1761-1768. (Pubitemid 351697951)