Eicosapentaenoic Acid Inhibits Oxidation of ApoB-containing Lipoprotein Particles of Different Size in Vitro When Administered Alone or in Combination with Atorvastatin Active Metabolite Compared with Other Triglyceride-lowering Agents

Journal of Cardiovascular Pharmacology

Volumn 68, Issue 1, 2016, Pages 33-40

  Mason, R Preston ^a,b   Sherratt, Samuel C R ^b   Jacob, Robert F ^b  

^a HARVARD MEDICAL SCHOOL   (United States)

^b ELUCIDA RESEARCH LLC   (United States)

Author keywords

atorvastatin; dense LDL; docosahexaenoic acid; eicosapentaenoic acid; omega 3 fatty acid; small; triglycerides

Indexed keywords

ALPHA TOCOPHEROL; ANTIOXIDANT; APOLIPOPROTEIN B; ATORVASTATIN; DOCOSAHEXAENOIC ACID; DRUG METABOLITE; FENOFIBRATE; GEMFIBROZIL; ICOSAPENTAENOIC ACID; LOW DENSITY LIPOPROTEIN; NICOTINIC ACID; VERY LOW DENSITY LIPOPROTEIN; APOB PROTEIN, HUMAN; APOLIPOPROTEIN B100; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE INHIBITOR; THIOBARBITURIC ACID REACTIVE SUBSTANCE; TRIACYLGLYCEROL;

ANTIOXIDANT ACTIVITY; ARTICLE; COMPARATIVE EFFECTIVENESS; CONTROLLED STUDY; DRUG DOSE; HUMAN; HUMAN EXPERIMENT; IC50; IN VITRO STUDY; LIPID OXIDATION; NORMAL HUMAN; PARTICLE SIZE; PHYSICAL CHEMISTRY; POTENTIAL DIFFERENCE; PRIORITY JOURNAL; COMBINATION DRUG THERAPY; COMPARATIVE STUDY; DOSE RESPONSE; DOWN REGULATION; METABOLISM; OXIDATION REDUCTION REACTION; TIME FACTOR;

ANTIOXIDANTS; APOLIPOPROTEIN B-100; ATORVASTATIN CALCIUM; DOSE-RESPONSE RELATIONSHIP, DRUG; DOWN-REGULATION; DRUG THERAPY, COMBINATION; EICOSAPENTAENOIC ACID; HUMANS; HYDROXYMETHYLGLUTARYL-COA REDUCTASE INHIBITORS; LIPOPROTEINS, LDL; LIPOPROTEINS, VLDL; OXIDATION-REDUCTION; PARTICLE SIZE; THIOBARBITURIC ACID REACTIVE SUBSTANCES; TIME FACTORS; TRIGLYCERIDES;

EID: 84960172706     PISSN: 01602446     EISSN: 15334023     Source Type: Journal    
DOI: 10.1097/FJC.0000000000000379     Document Type: Article

References (60)

1. Daviglus ML, Stamler J, Orencia AJ, et al. Fish consumption and the 30-year risk of fatal myocardial infarction. N Engl J Med. 1997;336: 1046-1053.
2. Mozaffarian D, Wu JH. Omega-3 fatty acids and cardiovascular disease: effects on risk factors, molecular pathways, and clinical events. J Am Coll Cardiol. 2011;58:2047-2067.
3. Calder PC. The role of marine omega-3 (n-3) fatty acids in inflammatory processes, atherosclerosis and plaque stability. Mol Nutr Food Res. 2012; 56:1073-1080.
4. Ballantyne CM, Bays HE, Kastelein JJ, et al. Efficacy and safety of eicosapentaenoic acid ethyl ester (AMR101) therapy in statin-treated patients with persistent high triglycerides (from the ANCHOR study). Am J Cardiol. 2012;110:984-992.
5. Bays HE, Ballantyne CM, Braeckman RA, et al. Icosapent ethyl, a pure ethyl ester of eicosapentaenoic acid: effects on circulating markers of inflammation from the MARINE and ANCHOR studies. Am J Cardiovasc Drugs. 2013;13:37-46.
6. Bays HE, Ballantyne CM, Kastelein JJ, et al. Eicosapentaenoic acid ethyl ester (AMR101) therapy in patients with very high triglyceride levels (from the Multi-center, plAcebo-controlled, Randomized, double-blINd, 12-week study with an open-label Extension [MARINE] trial). Am J Cardiol. 2011;108:682-690.
7. Braeckman RA, Manku MS, Bays HE, et al. Icosapent ethyl, a pure EPA omega-3 fatty acid: effects on plasma and red blood cell fatty acids in patients with very high triglyceride levels (results from the MARINE study). Prostaglandins Leukot Essent Fatty Acids. 2013;89:195-201.
8. Satoh N, Shimatsu A, Kotani K, et al. Purified eicosapentaenoic acid reduces small dense LDL, remnant lipoprotein particles, and C-reactive protein in metabolic syndrome. Diabetes Care. 2007;30:144-146.
9. Satoh-Asahara N, Shimatsu A, Sasaki Y, et al. Highly purified eicosapentaenoic acid increases interleukin-10 levels of peripheral blood monocytes in obese patients with dyslipidemia. Diabetes Care. 2012; 35:2631-2639.
10. Itakura H, Yokoyama M, Matsuzaki M, et al. Relationships between plasma fatty acid composition and coronary artery disease. J Atheroscler Thromb. 2011;18:99-107.
11. Yokoyama M, Origasa H, Matsuzaki M, et al. Effects of eicosapentaenoic acid on major coronary events in hypercholesterolaemic patients (JELIS): a randomised open-label, blinded endpoint analysis. Lancet. 2007;369:1090-1098.
12. Mita T, Watada H, Ogihara T, et al. Eicosapentaenoic acid reduces the progression of carotid intima-media thickness in patients with type 2 diabetes. Atherosclerosis. 2007;191:162-167.
13. Takaki A, Umemoto S, Ono K, et al. Add-on therapy of EPA reduces oxidative stress and inhibits the progression of aortic stiffness in patients with coronary artery disease and statin therapy: a randomized controlled study. J Atheroscler Thromb. 2011;18:857-866.
14. Sasaki J, Miwa T, Odawara M. Administration of highly purified eicosapentaenoic acid to statin-treated diabetic patients further improves vascular function. Endocr J. 2012;59:297-304.
15. Effects of extended-release niacin with laropiprant in high-risk patients. N Engl J Med. 2014;371:203-212.
16. Boden WE, Probstfield JL, Anderson T, et al. Niacin in patients with low HDL cholesterol levels receiving intensive statin therapy. N Engl J Med. 2011;365:2255-2267.
17. Ginsberg HN, Elam MB, Lovato LC, et al. Effects of combination lipid therapy in type 2 diabetes mellitus. N Engl J Med. 2010;362:1563-1574.
18. Davidson MH, Rosenson RS, Maki KC, et al. Effects of fenofibric acid on carotid intima-media thickness in patients with mixed dyslipidemia on atorvastatin therapy: randomized, placebo-controlled study (FIRST). Arterioscler Thromb Vasc Biol. 2014;34:1298-1306.
19. Mason RP, Jacob RF. Eicosapentaenoic acid inhibits glucose-induced membrane cholesterol crystalline domain formation through a potent antioxidant mechanism. Biochim Biophys Acta. 2015;1848:502-509.
20. Witztum JL. The oxidation hypothesis of atherosclerosis. Lancet. 1994; 344:793-795.
21. Steinberg D. Lewis A. Conner Memorial Lecture. Oxidative modification of LDL and atherogenesis. Circulation. 1997;95:1062-1071.
22. Chisolm GM, Steinberg D. The oxidative modification hypothesis of atherogenesis: an overview. Free Radic Biol Med. 2000;28: 1815-1826.
23. Ehara S, Ueda M, Naruko T, et al. Elevated levels of oxidized low density lipoprotein show a positive relationship with the severity of acute coronary syndromes. Circulation. 2001;103:1955-1960.
24. Holvoet P, Kritchevsky SB, Tracy RP, et al. The metabolic syndrome, circulating oxidized LDL, and risk of myocardial infarction in wellfunctioning elderly people in the health, aging, and body composition cohort. Diabetes. 2004;53:1068-1073.
25. Walter MF, Jacob RF, Jeffers B, et al. Serum levels of thiobarbituric acid reactive substances predict cardiovascular events in patients with stable coronary artery disease: a longitudinal analysis of the PREVENT study. J Am Coll Cardiol. 2004;44:1996-2002.
26. Rizzo M, Berneis K. Low-density lipoprotein size and cardiovascular risk assessment. QJM. 2006;99:1-14.
27. Ai M, Otokozawa S, Asztalos BF, et al. Small dense LDL cholesterol and coronary heart disease: results from the Framingham Offspring Study. Clin Chem. 2010;56:967-976.
28. Gardner CD, Fortmann SP, Krauss RM. Association of small low-density lipoprotein particles with the incidence of coronary artery disease in men and women. JAMA. 1996;276:875-881.
29. Hirano T, Ito Y, Koba S, et al. Clinical significance of small dense lowdensity lipoprotein cholesterol levels determined by the simple precipitation method. Arterioscler Thromb Vasc Biol. 2004;24:558-563.
30. Koba S, Hirano T, Ito Y, et al. Significance of small dense low-density lipoprotein-cholesterol concentrations in relation to the severity of coronary heart diseases. Atherosclerosis. 2006;189:206-214.
31. Anber V, Griffin BA, McConnell M, et al. Influence of plasma lipid and LDL-subfraction profile on the interaction between low density lipoprotein with human arterial wall proteoglycans. Atherosclerosis. 1996;124: 261-271.
32. Galeano NF, Al-Haideri M, Keyserman F, et al. Small dense low density lipoprotein has increased affinity for LDL receptor-independent cell surface binding sites: a potential mechanism for increased atherogenicity. J Lipid Res. 1998;39:1263-1273.
33. Krauss RM. Heterogeneity of plasma low-density lipoproteins and atherosclerosis risk. Curr Opin Lipidol. 1994;5:339-349.
34. Nigon F, Lesnik P, Rouis M, et al. Discrete subspecies of human low density lipoproteins are heterogeneous in their interaction with the cellular LDL receptor. J Lipid Res. 1991;32:1741-1753.
35. de Graaf J, Hak-Lemmers HL, Hectors MP, et al. Enhanced susceptibility to in vitro oxidation of the dense low density lipoprotein subfraction in healthy subjects. Arterioscler Thromb. 1991;11:298-306.
36. Tribble DL, Holl LG, Wood PD, et al. Variations in oxidative susceptibility among six low density lipoprotein subfractions of differing density and particle size. Atherosclerosis. 1992;93:189-199.
37. Tenenbaum A, Klempfner R, Fisman EZ. Hypertriglyceridemia: a too long unfairly neglected major cardiovascular risk factor. Cardiovasc Diabetol. 2014;13:159.
38. Mason RP, Walter MF, Day CA, et al. Active metabolite of atorvastatin inhibits membrane cholesterol domain formation by an antioxidant mechanism. J Biol Chem. 2006;281:9337-9345.
39. Aviram M, Rosenblat M, Bisgaier CL, et al. Atorvastatin and gemfibrozil metabolites, but not the parent drugs, are potent antioxidants against lipoprotein oxidation. Atherosclerosis. 1998;138:271-280.
40. Jacob RF, Walter MF, Self-Medlin Y, et al. Atorvastatin active metabolite inhibits oxidative modification of small dense low-density lipoprotein. J Cardiovasc Pharmacol. 2013;62:160-166.
41. Davies IG, Graham JM, Griffin BA. Rapid separation of LDL subclasses by iodixanol gradient ultracentrifugation. Clin Chem. 2003;49:1865-1872.
42. Braeckman RA, Stirtan WG, Soni PN. Pharmacokinetics of eicosapentaenoic acid in plasma and red blood cells after multiple oral dosing with icosapent ethyl in healthy subjects. Clin Pharmacol Drug Dev. 2014;3: 101-108.
43. Wagner AH, Kohler T, Ruckschloss U, et al. Improvement of nitric oxidedependent vasodilatation by HMG-CoA reductase inhibitors through attenuation of endothelial superoxide anion formation. Arterioscler Thromb Vasc Biol. 2000;20:61-69.
44. Mason RP, Walter MF, Jacob RF. Effects of HMG-CoA reductase inhibitors on endothelial function: role of microdomains and oxidative stress. Circulation. 2004;109(21 suppl 1):II34-II41.
45. Tsimikas S, Witztum JL, Miller ER, et al. High-dose atorvastatin reduces total plasma levels of oxidized phospholipids and immune complexes present on apolipoprotein B-100 in patients with acute coronary syndromes in the MIRACL trial. Circulation. 2004;110: 1406-1412.
46. Shishehbor MH, Brennan ML, Aviles RJ, et al. Statins promote potent systemic antioxidant effects through specific inflammatory pathways. Circulation. 2003;108:426-431.
47. Mason RP, Walter MF, Day CA, et al. Intermolecular differences of 3-hydroxy-3-methylglutaryl coenzyme a reductase inhibitors contribute to distinct pharmacologic and pleiotropic actions. Am J Cardiol. 2005;96: 11F-23F.
48. Kinlay S, Schwartz GG, Olsson AG, et al. Inflammation, statin therapy, and risk of stroke after an acute coronary syndrome in the MIRACL study. Arterioscler Thromb Vasc Biol. 2008;28:142-147.
49. Libby P. Inflammation in atherosclerosis. Nature. 2002;420:868-874.
50. Libby P, Ridker PM, Maseri A. Inflammation and atherosclerosis. Circulation. 2002;105:1135-1143.
51. Goldstein JL, Ho YK, Basu SK, et al. Binding site on macrophages that mediates uptake and degradation of acetylated low density lipoprotein, producing massive cholesterol deposition. Proc Natl Acad Sci U S A. 1979;76:333-337.
52. Parthasarathy S, Young SG, Witztum JL, et al. Probucol inhibits oxidative modification of low density lipoprotein. J Clin Invest. 1986;77:641-644.
53. Walter MF, Jacob RF, Bjork RE, et al. Circulating lipid hydroperoxides predict cardiovascular events in patients with stable coronary artery disease: the PREVENT study. J Am Coll Cardiol. 2008;51:1196-1202.
54. Hulthe J, Hulten LM, Fagerberg B. Low adipocyte-derived plasma protein adiponectin concentrations are associated with the metabolic syndrome and small dense low-density lipoprotein particles: atherosclerosis and insulin resistance study. Metabolism. 2003;52: 1612-1614.
55. Bays HE, Braeckman RA, Ballantyne CM, et al. Icosapent ethyl, a pure EPA omega-3 fatty acid: effects on lipoprotein particle concentration and size in patients with very high triglyceride levels (the MARINE study). J Clin Lipidol. 2012;6:565-572.
56. Ballantyne CM, Braeckman RA, Bays HE, et al. Effects of icosapent ethyl on lipoprotein particle concentration and size in statin-treated patients with persistent high triglycerides (the ANCHOR Study). J Clin Lipidol. 2015;9:377-383.
57. Brinton EA, Ballantyne CM, Bays HE, et al. Effects of icosapent ethyl on lipid and inflammatory parameters in patients with diabetes mellitus-2, residual elevated triglycerides (200-500 mg/dL), and on statin therapy at LDL-C goal: the ANCHOR study. Cardiovasc Diabetol. 2013;12:100.
58. Ando M, Sanaka T, Nihei H. Eicosapentanoic acid reduces plasma levels of remnant lipoproteins and prevents in vivo peroxidation of LDL in dialysis patients. J Am Soc Nephrol. 1999;10:2177-2184.
59. Tanaka N, Ishida T, Nagao M, et al. Administration of high dose eicosapentaenoic acid enhances anti-inflammatory properties of high-density lipoprotein in Japanese patients with dyslipidemia. Atherosclerosis. 2014;237:577-583.
60. Ando K, Watanabe T, Daidoji H, et al. Combination therapy of eicosapentaenoic acid and pitavastatin for coronary plaque regression evaluated by integrated backscatter intravascular ultrasonography: a randomized controlled trial. Circulation. 2015;132:A12007.