Antiatherosclerotic properties of EP2302, A novel squalene synthase inhibitor, in the cholesterol-fed rabbit

Journal of Cardiovascular Pharmacology

Volumn 51, Issue 6, 2008, Pages 573-580

  Tavridou, Anna ^a   Kaklamanis, Loukas ^b   Papalois, Apostolos ^c   Kourounakis, Angeliki P ^d   Rekka, Eleni A ^e   Kourounakis, Panos N ^e   Charalambous, Avgui ^c   Manolopoulos, Vangelis G ^a  

^a DEMOCRITUS UNIVERSITY OF THRACE   (Greece)

^b ONASSIS CARDIAC SURGERY CENTER   (Greece)

^c ELPEN Pharmaceutical Co Inc   (Greece)

^d UNIVERSITY OF ATHENS   (Greece)

^e ARISTOTLE UNIVERSITY OF THESSALONIKI   (Greece)

Author keywords

Atherosclerosis; Cholesterol fed rabbit; EP2302; Lipids; Nitric oxide donor; Squalene synthase inhibitor

Indexed keywords

ALANINE AMINOTRANSFERASE; ASPARTATE AMINOTRANSFERASE; CHOLESTEROL; EP 2302; HIGH DENSITY LIPOPROTEIN CHOLESTEROL; LOW DENSITY LIPOPROTEIN CHOLESTEROL; PLACEBO; SQUALENE SYNTHASE INHIBITOR; TRIACYLGLYCEROL; UNCLASSIFIED DRUG; ANTIOXIDANT; BIPHENYL DERIVATIVE; EP2302; LIPID; MORPHOLINE DERIVATIVE; SQUALENE SYNTHASE;

ALANINE AMINOTRANSFERASE BLOOD LEVEL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; ASCENDING AORTA; ASPARTATE AMINOTRANSFERASE BLOOD LEVEL; ATHEROSCLEROSIS; CHOLESTEROL BLOOD LEVEL; CHOLESTEROL DIET; CONTROLLED STUDY; DESCENDING AORTA; MALE; NONHUMAN; ORGAN; PRIORITY JOURNAL; RABBIT; TOXICITY; TRIACYLGLYCEROL BLOOD LEVEL; ANIMAL; AORTA; BLOOD; CORONARY ARTERY DISEASE; DIET; DISEASE MODEL; DRUG ANTAGONISM; DRUG EFFECT; PATHOPHYSIOLOGY;

ANIMALS; ANTIOXIDANTS; AORTA; BIPHENYL COMPOUNDS; CHOLESTEROL; CORONARY ARTERY DISEASE; DIET; DISEASE MODELS, ANIMAL; FARNESYL-DIPHOSPHATE FARNESYLTRANSFERASE; LIPIDS; MORPHOLINES; RABBITS;

EID: 53249135210     PISSN: 01602446     EISSN: None     Source Type: Journal    
DOI: 10.1097/FJC.0b013e31817885fe     Document Type: Article

References (33)

1. Hennekens CH. Increasing burden of cardiovascular disease: current knowledge and future directions for research on risk factors. Circulation. 1998;97:1095-1102.
2. Steinberg D, Parthasarathy S, Carew TE, et al. Beyond cholesterol. Modifications of low-density lipoprotein that increase its atherogenicity. N Engl J Med. 1989;320:915-924.
3. Napoli C, de Nigris F, Williams-Ignarro S, et al. Nitric oxide and atherosclerosis: an update. Nitric Oxide. 2006;15:265-279.
4. Bellosta S, Bernini F, Ferri N, et al. Direct vascular effects of HMG-CoA reductase inhibitors. Atherosclerosis. 1998;137(Suppl:S)101-109.
5. LaRosa JC, He J, Vupputuri S. Effect of statins on risk of coronary disease: a meta-analysis of randomized controlled trials. JAMA. 1999;282: 2340-2346.
6. Kornbrust DJ, MacDonald JS, Peter CP, et al. Toxicity of the HMG-coenzyme A reductase inhibitor, lovastatin, to rabbits. J Pharmacol Exp Ther. 1989;248:498-505.
7. Masters BA, Palmoski MJ, Flint OP, et al. In vitro myotoxicity of the 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, pravastatin, lovastatin, and simvastatin, using neonatal rat skeletal myocytes. Toxicol Appl Pharmacol. 1995;131:163-174.
8. Charlton-Menys V, Durrington PN. Squalene synthase inhibitors: clinical pharmacology and cholesterol-lowering potential. Drugs. 2007;67:11-16.
9. Hiyoshi H, Yanagimachi M, Ito M, et al. Effect of ER-27856, a novel squalene synthase inhibitor, on plasma cholesterol in rhesus monkeys: comparison with 3-hydroxy-3-methylglutaryl-coa reductase inhibitors. J Lipid Res. 2000;41:1136-1144.
10. Ugawa T, Kakuta H, Moritani H, Inagaki O. Effect of YM-53601, a novel squalene synthase inhibitor, on the clearance rate of plasma LDL and VLDL in hamsters. Br J Pharmacol. 2002;137:561-569.
11. Amano Y, Nishimoto T, Tozawa R, et al. Lipid-lowering effects of TAK-475, a squalene synthase inhibitor, in animal models of familial hypercholesterolemia. Eur J Pharmacol. 2003;466:155-161.
12. Nishimoto T, Amano Y, Tozawa R, et al. Lipid-lowering properties of TAK-475, a squalene synthase inhibitor, in vivo and in vitro. Br J Pharmacol. 2003;139:911-918.
13. Burnett JR. Drug evaluation: TAK-475-an oral inhibitor of squalene synthase for hyperlipidemia. Curr Opin Investig Drugs. 2006;7:850-856.
14. Chrysselis MC, Rekka EA, Kourounakis PN. Hypocholesterolemic and hypolipidemic activity of some novel morpholine derivatives with antioxidant activity. J Med Chem. 2000;43:609-612.
15. Chrysselis MC, Rekka EA, Siskou IC, Kourounakis PN. Nitric oxide releasing morpholine derivatives as hypolipidemic and antioxidant agents. J Med Chem. 2002;45:5406-5409.
16. Goss SP, Kalyanaraman B, Hogg N. Antioxidant effects of nitric oxide and nitric oxide donor compounds on low-density lipoprotein oxidation. Methods Enzymol. 1999;301:444-453.
17. Kurowska EM, Carroll KK. Hypocholesterolemic properties of nitric oxide. In vivo and in vitro studies using nitric oxide donors. Biochim Biophys Acta. 1998;1392:41-50.
18. Tavridou A, Manolopoulos VG. Antioxidant properties of two novel 2-biphenylmorpholine compounds (EP2306 and EP2302) in vitro and in vivo. Eur J Pharmacol. 2004;505:213-221.
19. Tavridou A, Kaklamanis L, Megaritis G, et al. Pharmacological characterization of EP2306 and EP2302, potent inhibitors of squalene synthase and lipid biosynthesis. Eur J Pharmacol. 2006;535:34-42.
20. Tavridou A, Kaklamanis L, Papalois A, et al. EP2306, a novel squalene synthase inhibitor, reduces atherosclerosis in the cholesterol-fed rabbit. J Pharmacol Exp Ther. 2007;323:794-804.
21. Yang BC, Phillips MI, Mohuczy D, et al. Increased angiotensin II type 1 receptor expression in hypercholesterolemic atherosclerosis in rabbits. Arterioscler Thromb Vasc Biol. 1998;18:1433-1439.
22. Sugano M, Makino N, Yanaga T. The effects of renin-angiotensin system inhibition on aortic cholesterol content in cholesterol-fed rabbits. Atherosclerosis. 1996;127:123-129.
23. Hernandez-Presa MA, Ortego M, Tunon J, et al. Simvastatin reduces NF-kappaB activity in peripheral mononuclear and in plaque cells of rabbit atheroma more markedly than lipid lowering diet. Cardiovasc Res. 2003; 57:168-177.
24. Alfon J, Guasch JF, Berrozpe M, Badimon L. Nitric oxide synthase II (NOS II) gene expression correlates with atherosclerotic intimal thickening. Preventive effects of HMG-CoA reductase inhibitors. Atherosclerosis. 1999;145:325-331.
25. Nachtigal P, Kopecky M, Solichova D, et al. The changes in the endothelial expression of cell adhesion molecules and iNOS in the vessel wall after the short-term administration of simvastatin in rabbit model of atherosclerosis. J Pharm Pharmacol. 2005;57:197-203.
26. Kano H, Hayashi T, Sumi D, et al. A HMG-CoA reductase inhibitor improved regression of atherosclerosis in the rabbit aorta without affecting serum lipid levels: possible relevance of up-regulation of endothelial NO synthase mRNA. Biochem Biophys Res Commun. 1999;259:414-419.
27. Sumi D, Hayashi T, Thakur NK, et al. A HMG-CoA reductase inhibitor possesses a potent anti-atherosclerotic effect other than serum lipid lowering effects - the relevance of endothelial nitric oxide synthase and superoxide anion scavenging action. Atherosclerosis. 2001;155:347-357.
28. Rikitake Y, Kawashima S, Takeshita S, et al. Anti-oxidative properties of fluvastatin, an HMG-CoA reductase inhibitor, contribute to prevention of atherosclerosis in cholesterol-fed rabbits. Atherosclerosis. 2001;154: 87-96.
29. Mitani H, Egashira K, Ohashi N, et al. Preservation of endothelial function by the HMG-CoA reductase inhibitor fluvastatin through its lipidlowering independent antioxidant properties in atherosclerotic rabbits. Pharmacology. 2003;68:121-130.
30. Herman AG, Moncada S. Therapeutic potential of nitric oxide donors in the prevention and treatment of atherosclerosis. Eur Heart J. 2005;26: 1945-1955.
31. Tavridou A, Megaritis G, Kourounakis AP, et al. EP2306 and EP2302, two novel squalene synthase inhibitors, stimulate endothelial nitric oxide expression in cultured endothelial cells. Endothelium. 2007;14:239-243.
32. Farmer JA, Gotto AM, Jr. Dyslipidemia and the vulnerable plaque. Prog Cardiovasc Dis. 2002;44:415-428.
33. Williams KJ, Feig JE, Fisher EA. Cellular and molecular mechanisms for rapid regression of atherosclerosis: from bench top to potentially achievable clinical goal. Curr Opin Lipidol. 2007;18:443-450.