Varespladib (A-002), a secretory phospholipase A2 inhibitor, reduces atherosclerosis and aneurysm formation in ApoE-/- mice

Journal of Cardiovascular Pharmacology

Volumn 53, Issue 1, 2009, Pages 60-65

  Fraser, Heather ^a   Hislop, Colin ^a   Christie, Robert M ^b   Rick, Heather L ^b   Reidy, Charles A ^b   Chouinard, Michael L ^b   Eacho, Patrick I ^b   Gould, Kenneth E ^b   Trias, Joaquim ^a  

^a Anthera Pharmaceuticals Inc   (United States)

^b ELI LILLY AND COMPANY   (United States)

Author keywords

A 002; Aneurysm; ApoE ; Atherosclerosis; Cholesterol; sPLA 2; Varespladib

Indexed keywords

A 001; A 002; ANGIOTENSIN II; APOLIPOPROTEIN E; CHOLESTEROL; PHOSPHOLIPASE A2 GROUP II; PHOSPHOLIPASE A2 GROUP IIA; PHOSPHOLIPASE A2 GROUP IV; PHOSPHOLIPASE A2 GROUP V; PHOSPHOLIPASE A2 GROUP X; PHOSPHOLIPASE A2 INHIBITOR; UNCLASSIFIED DRUG; VARESPLADIB; ACETIC ACID DERIVATIVE; INDOLE DERIVATIVE; PLA2G2A PROTEIN, HUMAN; PLA2G2A PROTEIN, MOUSE; PLASMA PROTEIN; PLIALPHA; SECRETORY PHOSPHOLIPASE A2;

ANEURYSM; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; AORTA ANEURYSM; AORTA ATHEROSCLEROSIS; ARTICLE; CARDIOVASCULAR EFFECT; CHOLESTEROL BLOOD LEVEL; CONTROLLED STUDY; DRUG BLOOD LEVEL; DRUG EFFECT; ENZYME INHIBITION; EXPERIMENTAL MODEL; IC 50; MALE; MOUSE; NONHUMAN; PRIORITY JOURNAL; ANIMAL; ANTAGONISTS AND INHIBITORS; AORTA; ARTERIOSCLEROSIS; ATHEROSCLEROSIS; C57BL MOUSE; DEFICIENCY; ENZYMOLOGY; GENETICS; HUMAN; KNOCKOUT MOUSE; PATHOLOGY; TRANSGENIC MOUSE;

ACETATES; ANEURYSM; ANIMALS; AORTA; APOLIPOPROTEINS E; ARTERIOSCLEROSIS; ATHEROSCLEROSIS; BLOOD PROTEINS; CHOLESTEROL; GROUP II PHOSPHOLIPASES A2; HUMANS; INDOLES; MALE; MICE; MICE, INBRED C57BL; MICE, KNOCKOUT; MICE, TRANSGENIC; PHOSPHOLIPASES A2, SECRETORY;

EID: 60249099795     PISSN: 01602446     EISSN: None     Source Type: Journal    
DOI: 10.1097/FJC.0b013e318195bfbc     Document Type: Article

References (36)

1. Murakami M, Kudo I. Secretory phospholipase A2. Biol Pharm Bull. 2004;27:1158-1164.
2. Schaloske RH, Dennis EA. The phospholipase A2 superfamily and its group numbering system. Biochim Biophys Acta. 2006;1761:1246-1259.
3. Kimura-Matsumoto M, Ishikawa Y, Komiyama K, et al. Expression of secretory phospholipase A2s in human atherosclerosis development. Atherosclerosis. 2008;196:81-91.
4. Antonio V, Brouillet A, Janvier B, et al. Transcriptional regulation of the rat type IIA phospholipase A2 gene by cAMP and interleukin-1beta in vascular smooth muscle cells: interplay of the CCAAT/enhancer binding protein (C/EBP), nuclear factor-kappaB and Ets transcription factors. Biochem J. 2002;368:415-424. (Pubitemid 35454520)
5. de Beer FC, Webb NR. Inflammation and atherosclerosis: Group IIa and Group V sPLA2 are not redundant. Arterioscler Thromb Vasc Biol. 2006; 26:1421-1422.
6. Rosengren B, Jönsson-Rylander AC, Peilot H, et al. Distinctiveness of secretory phospholipase A2 group IIA and V suggesting unique roles in atherosclerosis. Biochim Biophys Acta. 2006;1761:1301-1308. (Pubitemid 44768005)
7. Webb NR. Secretory phospholipase A2 enzymes in atherogenesis. Curr Opin Lipidol. 2005;16:341-344.
8. Rosengren B, Peilot H, Umaerus M, et al. Secretory phospholipase A2 group V: lesion distribution, activation by arterial proteoglycans, and induction in aorta by aWestern diet. Arterioscler Thromb Vasc Biol. 2006; 26:1579-1585. (Pubitemid 44288986)
9. Hanasaki K, Yamada K, Yamamoto S, et al. Potent modification of low density lipoprotein by group X secretory phospholipase A2 is linked to macrophage foam cell formation. J Biol Chem. 2002;277:29116-29124.
10. Wootton PT, Drenos F, Cooper JA, et al. Tagging-SNP haplotype analysis of the secretory PLA2IIa gene PLA2G2A shows strong association with serum levels of sPLA2IIa: results from the UDACS study. Hum Mol Genet. 2006;J15:355-361. (Pubitemid 43125989)
11. Wootton PT, Arora NL, Drenos F, et al. Tagging SNP haplotype analysis of the secretory PLA2-V gene, PLA2G5, shows strong association with LDL and oxLDL levels, suggesting functional distinction from sPLA2- IIA: results from the UDACS study. Hum Mol Genet. 2007;16: 1437-1444. (Pubitemid 47061339)
12. Bostrom MA, Boyanovsky BB, Jordan CT, et al. Group V secretory phospholipase A2 promotes atherosclerosis. Evidence from genetically altered mice. Arterioscler Thromb Vasc Biol. 2007;27:445-447.
13. Ivandic B, Castellani LW, Wang XP, et al. Role of group II secretory phospholipase A2 in atherosclerosis: 1. increased atherogenesis and altered lipoproteins in transgenic mice expressing group IIa phospholipase A2. Arterioscler Thromb Vasc Biol. 1999;19:1284-1290. (Pubitemid 29227649)
14. Anthonsen MW, Stengel D, Hourton D, et al. Mildly oxidized LDL induces expression of group IIa secretory phospholipase A2 in human monocyte-derived macrophages. Arterioscler Thromb Vasc Biol. 2000;20: 1276-1282. (Pubitemid 30262928)
15. Wooton-Kee CR, Boyanovsky BB, Nasser MS, et al. Group V sPLA2 hydrolysis of low-density lipoprotein results in spontaneous particle aggregation and promotes macrophage foam cell formation. Arterioscler Thromb Vasc Biol. 2004;24:762-767.
16. Pruzanski W, Stefanski E, de Beer FC, et al. Lipoproteins are substrates for normal secretory group IIA phospholipase A2: preferential hydrolysis of acute phase HDL. J Lipid Res. 1998;39:2150-2160. (Pubitemid 28523121)
17. Hakala JK, Oorni K, Pentikainen MO, et al. Lipolysis of LDL by human secretory phospholipase A(2) induces particle fusion and enhances the retention of LDL to human aortic proteoglycans. Arterioscler Thromb Vasc Biol. 2001;21:1053-1058.
18. Reid RC. Inhibitors of secretory phospholipase A2 group IIA. Curr Med Chem. 2005;12:3011-3026.
19. Schevitz RW, Bach NJ, Carlson DG, et al. Structure-based design of the first potent and selective inhibitor of human non-pancreatic secretory phospholipase A2. Nat Struct Biol. 1995;2:458-465.
20. Draheim SE, Bach NJ, Dillard RD, et al. Indole inhibitors of human nonpancreatic secretory phospholipase A2. 3. Indole-3-glyoxamides. J Med Chem. 1996;39:5159-5175.
21. Fox N, Song M, Schrementi J, et al. Transgenic model for the discovery of novel human secretory non-pancreatic phospholipase A2 inhibitors. Eur J Pharmacol. 1996;308:195-203. (Pubitemid 26237047)
22. Snyder DW, Bach NJ, Dillard RD, et al. Pharmacology of A-001/S-5920, [[3-(aminooxoacetyl)-2-ethyl-1-(phenylmethyl)-1H-indol-4-yl]oxy] acetate, a potent and selective secretory phospholipase A2 inhibitor: a new class of anti-inflammatory drugs, SPI. J Pharmacol Exp Ther. 1999;288: 1117-1124.
23. Plump AS, Smith JD, Hayek T, et al. Severe hypercholesterolemia and atherosclerosis in apolipoprotein E-deficient mice created by homologous recombination in ES cells. Cell. 1992;71:343-353.
24. Daugherty A, Manning MW, Cassis LA. Angiotensin II promotes atherosclerotic lesions and aneurysms in apolipoprotein E-deficient mice. J Clin Invest. 2000;105:1605-1612. (Pubitemid 30390311)
25. Grainger DJ, Reckless J, McKilligin E. Apolipoprotein E modulates clearance of apoptotic bodies in vitro and in vivo, resulting in a systemic proinflammatory state in apolipoprotein E-deficient mice. J Immunol. 2004;173:6366-6375. (Pubitemid 39487796)
26. Ali K, Middleton M, Puré E, et al. Apolipoprotein E suppresses the type I inflammatory response in vivo. Circ Res. 2005;97:922-927. (Pubitemid 41552678)
27. Ghesquiere SA, Gijbels MJ, Anthonsen M, et al. Macrophage-specific overexpression of group IIa sPLA2 increases atherosclerosis and enhances collagen deposition. J Lipid Res. 2005;46:201-210. (Pubitemid 40271083)
28. MacPhee M, Chepenik KP, Liddell RA, et al. The secretory phospholipase A2 gene is a candidate for the Mom1 locus, a major modifier of ApcMininduced intestinal neoplasia. Cell. 1995;81:957-966.
29. Zadelaar S, Kleemann R, Verschuren L, et al. Mouse models for atherosclerosis and pharmaceutical modifiers. Arterioscler Thromb Vasc Biol. 2007;27:1706-1721. (Pubitemid 47207165)
30. Nobuhiko A, Suganuma E, Babaev VR, et al. Angiotensin II amplifies macrophage-driven atherosclerosis. Arterioscler Thromb Vasc Biol. 2004; 11:2143-2148.
31. Keidar S, Kaplan M, Hoffman A, et al. Ang-II stimulates macrophage-mediated oxidation of LDL. Atherosclerosis. 1995;115: 201-215.
32. NiW, Kitamoto S, Ishibashi M, et al. Monocyte chemoattractant protein-1 is an essential inflammatory mediator in angiotensin II-induced progression of established atherosclerosis in hypercholesterolemic mice. Arterioscler Thromb Vasc Biol. 2004;24:534-539. (Pubitemid 38326149)
33. Choke E, Cockerill G, Wilson WR, et al. A review of biological factors implicated in abdominal aortic aneurysm rupture. Eur J Vasc Endovasc Surg. 2005;30:227-244. (Pubitemid 41086292)
34. Holmes DR, Wester W, Thompson RW, et al. Prostaglandin E2 synthesis and cyclooxygenase expression in abdominal aortic aneurysms. J Vasc Surg. 1997;25:810-815. (Pubitemid 27227676)
35. King VL, Trivedi DB, Gitlin JM, et al. Selective cyclooxygenase-2 inhibition with celecoxib decreases angiotensin II-induced abdominal aortic aneurysm formation in mice. Arterioscler Thromb Vasc Biol. 2006; 26:1137-1143. (Pubitemid 43732124)
36. Eagleton MJ, Ballard N, Lynch E, et al. Early increased MT1-MMP expression and late MMP-2 and MMP-9 activity during angiotensin II induced aneurysm formation. J Surg Res. 2006;135:345-351. (Pubitemid 44414882)