EP2306 and EP2302, two novel squalene synthase inhibitors, stimulate endothelial nitric oxide synthase expression in cultured endothelial cells

Endothelium: Journal of Endothelial Cell Research

Volumn 14, Issue 4-5, 2007, Pages 239-243

  Tavridou, Anna ^a   Megaritis, George ^b   Kourounakis, Angeliki ^c   Charalambous, Avgui ^b   Manolopoulos, Vangelis ^a  

^a DEMOCRITUS UNIVERSITY OF THRACE   (Greece)

^b ELPEN Pharmaceutical Co Inc   (Greece)

^c UNIVERSITY OF ATHENS   (Greece)

Author keywords

Atherosclerosis; BAE Cells; CPAE Cells; Endothelial Nitric Oxide Synthase; Squalene Synthase Inhibitor

Indexed keywords

2 (4 BIPHENYL) 2 (3 NITROOXYPROPOXY) 4 METHYLMORPHINE HYDROBROMIDE; 2 (4 BIPHENYL) 4 METHYLOCTAHYDRO 1,4 BENZOXAZIN 2 OL HYDROBROMIDE; ARGININE; CITRULLINE; ENDOTHELIAL NITRIC OXIDE SYNTHASE; EP 2302; EP 2306; SQUALENE SYNTHASE INHIBITOR; UNCLASSIFIED DRUG;

ANIMAL CELL; ANTIOXIDANT ACTIVITY; ARTICLE; ATHEROSCLEROSIS; CELL ADHESION; CELL FUNCTION; CELL PROLIFERATION; CELL PROTECTION; CELL STIMULATION; CONTROLLED STUDY; DRUG MECHANISM; DRUG STRUCTURE; ENDOTHELIUM CELL; ENZYME ACTIVITY; GENE EXPRESSION; IMMUNOASSAY; NONHUMAN; PRIORITY JOURNAL; THROMBOCYTE AGGREGATION;

ANIMALS; BIPHENYL COMPOUNDS; CATTLE; CELLS, CULTURED; ENDOTHELIAL CELLS; FARNESYL-DIPHOSPHATE FARNESYLTRANSFERASE; MORPHOLINES; NITRIC OXIDE SYNTHASE TYPE III;

BOVINAE;

EID: 35148864536     PISSN: 10623329     EISSN: 10292373     Source Type: Journal    
DOI: 10.1080/10623320701547216     Document Type: Article

References (28)

1. Bult, H., Herman, A. G. and Matthys, K. E. (1999) Antiatherosclerotic activity of drugs in relation to nitric oxide function. European Journal of Pharmacology, 375, pp. 157-176.
2. Burnett, J. R. (2006) Drug evaluation: TAK-475 - An oral inhibitor of squalene synthase for hyperlipidemia. Current Opinion in Investigational Drugs, 7, pp. 850-856.
3. Busse, R. and Mulsch, A. (1990) Calcium-dependent nitric oxide synthesis in endothelial cytosol is mediated by calmodulin. FEBS Letters, 265, pp. 133-136.
4. Charlton-Menys, V. and Durrington, P. N. (2007) Squalene synthase inhibitors: Clinical pharmacology and cholesterol-lowering potential. Drugs, 67, pp. 11-16.
5. Chrysselis, M. C., Rekka, E. A. and Kourounakis, P. N. (2000) Hypocholesterolemic and hypolipidemic activity of some novel morpholine derivatives with antioxidant activity. Journal of Medicinal Chemistry, 43, pp. 609-612.
6. Chrysselis, M. C., Rekka, E. A., Siskou, I. C. and Kourounakis, P. N. (2002) Nitric oxide releasing morpholine derivatives as hypolipidemic and antioxidant agents. Journal of Medicinal Chemistry, 45, pp. 5406-5409.
7. Feron, O., Belhassen, L., Kobzik, L., Smith, T. W., Kelly, R. A. and Michel, T. (1996) Endothelial nitric oxide synthase targeting to caveolae. Specific interactions with caveolin isoforms in cardiac myocytes and endothelial cells. Journal of Biological Chemistry, 271, pp. 22810-22814.
8. Forstermann, U., Pollock, J. S., Schmidt, H. H., Heller, M. and Murad, F. (1991) Calmodulin-dependent endothelium-derived relaxing factor/ nitric oxide synthase activity is present in the particulate and cytosolic fractions of bovine aortic endothelial cells. Proceedings of the National Academy of Sciences of the United States of America, 88, pp. 1788-1792.
9. Fulton, D., Gratton, J. -P. and Sessa, W. C. (2001) Post-translational control of endothelial nitric oxide synthase: Why isn't calcium/ calmodulin enough?. Journal of Pharmacology and Experimental Therapeutics, 299, pp. 818-824.
10. García-Cardeña, G., Fan, R., Stern, D. F., Liu, J. and Sessa, W. C. (1996) Endothelial nitric oxide is regulated by tyrosine phosphorylation and interacts with caveolin-1. Journal of Biological Chemistry, 271, pp. 27237-27240.
11. Hernandez-Perera, O., Perez-Sala, D. and Navarro-Antolin, J. (1998) Effects of the 3-hydroxy-3-methylglutaryl-CoA reductase inhibitors, atorvastatin and simvastatin, on the expression of endothelin-1 and endothelial nitric oxide synthase in vascular endothelial cells. Journal of Clinical Investigation, 101, pp. 2711-2719.
12. Hiyoshi, H., Yanagimachi, M., Ito, M., Ohtsuka, I., Yoshida, I., Saeki, T. and Tanaka, H. (2000) Effect of ER-27856, a novel squalene synthase inhibitor, on plasma cholesterol in rhesus monkeys: Comparison with 3-hydroxy-3-methylglutaryl-coa reductase inhibitors. Journal of Lipid Research, 41, pp. 1136-1144.
13. Ignarro, L. J. (1990) Biosynthesis and metabolism of endothelium-derived nitric oxide. Annual Reviews of Pharmacology and Toxicology, 30, pp. 535-560.
14. Ju, H., Venema, V. J., Marrero, M. B. and Venema, R. C. (1998) Inhibitory interactions of the bradykinin B2 receptor with endothelial nitric-oxide synthase. Journal of Biological Chemistry, 273, pp. 24025-24029.
15. Ju, H., Zou, R., Venema, V. J. and Venema, R. C. (1997) Direct interaction of endothelial nitric-oxide synthase and caveolin-1 inhibits synthase activity. Journal of Biological Chemistry, 272, pp. 18522-18525.
16. Kawashima, S. and Yokoyama, M. (2004) Dysfunction of endothelial nitric oxide synthase and atherosclerosis. Arteriosclerosis Thrombosis and Vascular Biology, 24, pp. 998-1005.
17. Laufs, U. (2003) Beyond lipid-lowering: Effects of statins on endothelial nitric oxide. European Journal of Clinical Pharmacology, 58, pp. 719-731.
18. Laufs, U., Fata, V. L., Plutzky, J. and Liao, J. K. (1998) Upregulation of endothelial nitric oxide synthase by HMG CoA reductase inhibitors. Circulation, 97, pp. 1129-1135.
19. Li, D. and Mehta, J. L. (2003) 3-Hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors protect against oxidized low-density lipoprotein-induced endothelial dysfunction. Endothelium, 10, pp. 17-21.
20. Liao, J. K., Shin, W. S. and Lee, W. Y. (1995) Oxidized low-density lipoprotein decreases the expression of endothelial nitric oxide synthase. Journal of Biological Chemistry, 270, pp. 319-324.
21. Michel, T. and Feron, O. (1997) Nitric oxide synthases: Which, where, how, and why?. Journal of Clinical Investigation, 100, pp. 2146-2152.
22. Moncada, S., Palmer, R. M. and Higgs, E. A. (1991) Nitric oxide: Physiology, pathophysiology, and pharmacology. Pharmacological Reviews, 43, pp. 109-142.
23. Napoli, C., de Negris, F., Williams-Ignarro, S., Pignalosa, O., Sica, V. and Ignarro, L. J. (2006) Nitric oxide and atherosclerosis: An update. Nitric Oxide, 15, pp. 265-279.
24. Nishimoto, T., Amano, Y., Tozawa, R., Ishikawa, E., Imura, Y., Yukimasa, H. and Sugiyama, Y. (2003) Lipid-lowering properties of TAK-475, a squalene synthase inhibitor, in vivo and in vitro. British Journal of Pharmacology, 139, pp. 911-918.
25. Tavridou, A., Kaklamanis, L., Megaritis, G., Kourounakis, A. P., Papalois, A., Roukounas, D., Rekka, E. A., Kourounakis, P. N., Charalambous, A. and Manolopoulos, V. G. (2006) Pharmacological characterization of EP2306 and EP2302, potent inhibitors of squalene synthase and lipid biosynthesis. European Journal of Pharmacology, 535, pp. 34-42.
26. Tavridou, A. and Manolopoulos, V. G. (2004) Antioxidant properties of two novel 2-biphenylmorpholine compounds (EP2306 and EP2302) in vitro and in vivo. European Journal of Pharmacology, 505, pp. 213-221.
27. Ugawa, T., Kakuta, H., Moritani, H. and Inagaki, O. (2002) Effect of YM-53601, a novel squalene synthase inhibitor, on the clearance rate of plasma LDL and VLDL in hamsters. British Journal of Pharmacology, 137, pp. 561-569.
28. Witztum, J. L. and Steiberg, D. (1991) Role of oxidized low-density lipoprotein in atherogenesis. Journal of Clinical Investigation, 88, pp. 1785-1792.