Identical LDL-cholesterol lowering but non-identical effects on NF-κB activity: High dose simvastatin vs combination therapy with ezetimibe

Atherosclerosis

Volumn 223, Issue 1, 2012, Pages 190-196

  Rudofsky, Gottfried ^a   Reismann, Peter ^a   Groener, Jan B ^a   Djuric, Zdenka ^a   Fleming, Thomas ^a   Metzner, Cornelia ^a   Grafe, Ingo A ^a   Bierhaus, Angelika ^a   Nawroth, Peter P ^a  

^a UNIVERSITY OF HEIDELBERG   (Germany)

Author keywords

Coadministration; Ezetimibe; LDL cholesterol; Nuclear factor kappa B; Simvastatin

Indexed keywords

C REACTIVE PROTEIN; EZETIMIBE; HYPOCHOLESTEROLEMIC AGENT; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; INSULIN; INTERLEUKIN 6; LOW DENSITY LIPOPROTEIN CHOLESTEROL; ORAL ANTIDIABETIC AGENT; SIMVASTATIN;

ADULT; AGED; ANTIINFLAMMATORY ACTIVITY; ARTICLE; CHOLESTEROL BLOOD LEVEL; CHOLESTEROL LOWERING ACTIVITY; CLINICAL ARTICLE; CONTROLLED STUDY; DOUBLE BLIND PROCEDURE; DRUG EFFECT; DRUG EFFICACY; DRUG MECHANISM; DRUG MEGADOSE; ENZYME LINKED IMMUNOSORBENT ASSAY; FEMALE; GEL MOBILITY SHIFT ASSAY; HUMAN; HUMAN CELL; HYPERCHOLESTEROLEMIA; LOW DRUG DOSE; MALE; NON INSULIN DEPENDENT DIABETES MELLITUS; PERIPHERAL BLOOD MONONUCLEAR CELL; PRIORITY JOURNAL; PROTEIN BINDING; PROTEIN BLOOD LEVEL; PROTEIN FUNCTION; PROTEIN INDUCTION; RANDOMIZED CONTROLLED TRIAL; TREATMENT OUTCOME;

AGED; ANTI-INFLAMMATORY AGENTS; AZETIDINES; BIOLOGICAL MARKERS; C-REACTIVE PROTEIN; CHOLESTEROL, LDL; DIABETES MELLITUS, TYPE 2; DOUBLE-BLIND METHOD; DOWN-REGULATION; DRUG COMBINATIONS; ELECTROPHORETIC MOBILITY SHIFT ASSAY; ENZYME-LINKED IMMUNOSORBENT ASSAY; FEMALE; GERMANY; HUMANS; HYDROXYMETHYLGLUTARYL-COA REDUCTASE INHIBITORS; HYPERCHOLESTEROLEMIA; INFLAMMATION; INFLAMMATION MEDIATORS; INTERLEUKIN-6; MALE; MIDDLE AGED; NF-KAPPA B; SIMVASTATIN; TIME FACTORS; TREATMENT OUTCOME;

EID: 84863085412     PISSN: 00219150     EISSN: 18791484     Source Type: Journal    
DOI: 10.1016/j.atherosclerosis.2012.04.003     Document Type: Article

References (30)

1. Ridker P.M., Danielson E., Fonseca F.A., Genest J., Gotto A.M., Kastelein J.J., et al. Reduction in C-reactive protein and LDL cholesterol and cardiovascular event rates after initiation of rosuvastatin: a prospective study of the JUPITER trial. Lancet 2009, 373:1175-1182. JUPITER Trial Study Group.
2. Baigent C., Blackwell L., Emberson J., Holland L.E., Reith C., Bhala N., et al. Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170,000 participants in 26 randomised trials. Lancet 2010, 376:1670-1681. Cholesterol Treatment Trialists' (CTT) Collaboration.
3. Biasucci L.M., Biasillo G., Stefanelli A. Inflammatory markers, cholesterol and statins: pathophysiological role and clinical importance. Clin Chem Lab Med 2010, 48:1685-1691.
4. Tuomisto T.T., Lumivuori H., Kansanen E., Häkkinen S.K., Turunen M.P., van Thienen J.V., et al. Simvastatin has an anti-inflammatory effect on macrophages via upregulation of an atheroprotective transcription factor, Kruppel-like factor 2. Cardiovasc Res 2008, 78:175-184.
5. Preusch M.R., Vanakaris A., Bea F., Ieronimakis N., Shimizu T., Konstandin M., et al. Rosuvastatin reduces neointima formation in a rat model of balloon injury. Eur J Med Res 2010, 15:461-467.
6. Devaraj S., Chan E., Jialal I. Direct demonstration of an antiinflammatory effect of simvastatin in subjects with the metabolic syndrome. J Clin Endocrinol Metab 2006, 91:4489-4496.
7. Rosenblum S.B., Huynh T., Afonso A., Davis H.R., Yumibe N., Clader J.W., et al. Discovery of 1-(4-fluorophenyl)-(3R)-[3-(4-fluorophenyl)-(3S)-hydroxypropyl]-(4S)-(4-hydroxyphenyl)-2-azetidinone (SCH 58235): a designed, potent, orally active inhibitor of cholesterol absorption. J Med Chem 1998, 41:973-980.
8. Ballantyne C.M., Houri J., Notarbartolo A., Melani L., Lipka L.J., Suresh R., et al. Effect of ezetimibe coadministered with atorvastatin in 628 patients with primary hypercholesterolemia: a prospective, randomized, double-blind trial. Circulation 2003, 107:2409-2415. Ezetimibe Study Group.
9. Dujovne C.A., Suresh R., McCrary Sisk C., Maccubbin D., Strony J., Veltri E. Safety and efficacy of ezetimibe monotherapy in 1624 primary hypercholesterolaemic patients for up to 2 years. Int J Clin Pract 2008, 62:1332-1336.
10. Cannon C.P., Giugliano R.P., Blazing M.A., Harrington R.A., Peterson J.L., Sisk C.M., et al. Rationale and design of IMPROVE-IT (IMProved Reduction of Outcomes: Vytorin Efficacy International Trial): comparison of ezetimbe/simvastatin versus simvastatin monotherapy on cardiovascular outcomes in patients with acute coronary syndromes. Am Heart J 2008, 156:826-832. IMPROVE-IT Investigators.
11. Kalogirou M., Tsimihodimos V., Elisaf M. Pleiotropic effects of ezetimibe: do they really exist?. Eur J Pharmacol 2010, 633:62-70.
12. Araujo D.B., Bertolami M.C., Ferreira W.P., Abdalla D.S., Faludi A.A., Nakamura Y., et al. Pleiotropic effects with equivalent low-density lipoprotein cholesterol reduction: comparative study between simvastatin and simvastatin/ezetimibe coadministration. J Cardiovasc Pharmacol 2010, 55:1-5.
13. Kater A.L., Batista M.C., Ferreira S.R. Improved endothelial function with simvastatin but unchanged insulin sensitivity with simvastatin or ezetimibe. Metabolism 2010, 59:921-926.
14. Landmesser U., Bahlmann F., Mueller M., Spiekermann S., Kirchhoff N., Schulz S., et al. Simvastatin versus ezetimibe: pleiotropic and lipid-lowering effects on endothelial function in humans. Circulation 2005, 111:2356-2363.
15. Kutuk O., Basaga H. Inflammation meets oxidation: NF-kappaB as a mediator of initial lesion development in atherosclerosis. Trends Mol Med 2003, 9:549-557.
16. Rudofsky G., Reismann P., Grafe I.A., Konrade I., Djuric Z., Tafel J., et al. Improved vascular function upon pioglitazone treatment in type 2 diabetes is not associated with changes in mononuclear NF-kappaB binding activity. Horm Metab Res 2007, 39:665-671.
17. Davidson M.H., McGarry T., Bettis R., Melani L., Lipka L.J., LeBeaut A.P., et al. Ezetimibe coadministered with simvastatin in patients with primary hypercholesterolemia. J Am Coll Cardiol 2002, 40:2125-2134.
18. Bradford M.M. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 1996, 72:248-254.
19. Baigent C., Landray M.J., Reith C., Emberson J., Wheeler D.C., Tomson C., et al. The effects of lowering LDL cholesterol with simvastatin plus ezetimibe in patients with chronic kidney disease (Study of Heart and Renal Protection): a randomised placebo-controlled trial. Lancet 2011, 377:2181-2192. SHARP Investigators.
20. Lazzerini P.E., Lorenzini S., Selvi E., Capecchi P.L., Chindamo D., Bisogno S., et al. Simvastatin inhibits cytokine production and nuclear factor-kB activation in interleukin 1beta-stimulated synoviocytes from rheumatoid arthritis patients. Clin Exp Rheumatol 2007, 25:696-700.
21. Hernández-Presa M.A., Ortego M., Tuñón J., Martín-Ventura J.L., Mas S., Blanco-Colio L.M., 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.
22. Hilgendorff A., Muth H., Parviz B., Staubitz A., Haberbosch W., Tillmanns H., et al. Statins differ in their ability to block NF-kappaB activation in human blood monocytes. Int J Clin Pharmacol Ther 2003, 41:397-401.
23. Noma K., Rikitake Y., Oyama N., Yan G., Alcaide P., Liu P.Y., et al. ROCK1 mediates leukocyte recruitment and neointima formation following vascular injury. J Clin Invest 2008, 118:1632-1644.
24. Liao J.K. Isoprenoids as mediators of the biological effects of statins. J Clin Invest 2002, 110:285-288.
25. Rodriguez P.L., Sahay S., Olabisi O.O., Whitehead I.P. ROCK I-mediated activation of NF-kappaB by RhoB. Cell Signal 2007, 19:2361-2369.
26. Liu P.Y., Liu Y.W., Lin L.J., Chen J.H., Liao J.K. Evidence for statin pleiotropy in humans: differential effects of statins and ezetimibe on rho-associated coiled-coil containing protein kinase activity, endothelial function, and inflammation. Circulation 2009, 119:131-138.
27. Rikitake Y., Liao J.K. ROCKs as therapeutic targets in cardiovascular diseases. Expert Rev Cardiovasc Ther 2005, 3:441-451.
28. Pearson T.A., Ballantyne C.M., Veltri E., Shah A., Bird S., Lin J., et al. Pooled analyses of effects on C-reactive protein and low density lipoprotein cholesterol in placebo-controlled trials of ezetimibe monotherapy or ezetimibe added to baseline statin therapy. Am J Cardiol 2009, 103:369-374.
29. Donath M.Y., Shoelson S.E. Type 2 diabetes as an inflammatory disease. Nat Rev Immunol 2011, 11:98-107.
30. Helenius M., Hänninen M., Lehtinen S.K., Salminen A. Changes associated with aging and replicative senescence in the regulation of transcription factor nuclear factor-kappa B. Biochem J 1996, 318:603-608.