Advances in Clinical and Experimental Medicine
2016, vol. 25, nr 3, May-June, p. 433–439
Publication type: original article
The Effect of Combined Ezetimibe/Atorvastatin Therapy vs. Atorvastatin Monotherapy on the Erythrocyte Membrane Structure in Patients with Coronary Artery Disease: A Pilot Study
1 Department of Internal Diseases and Clinical Pharmacology, Medical University of Łódź, Poland
2 Department of Environment Pollution Biophysics, Faculty of Biology and Environmental Protection, University of Łódź, Poland
Background. Erythrocytes play an important role in atherogenesis. An excessive accumulation of cholesterol in erythrocyte membranes leads to disruption of the erythrocytes.
Objectives. The aim of the study was to compare the effect of two different hypolipidemic therapies on the structure of erythrocyte membranes.
Material and Methods. The study included 18 patients with angiographic confirmed coronary artery disease who, despite at least 6 months of hypolipidemic treatment, had not achieved LDL-C < 70 mg/dL and 18 healthy individuals as the control group. The following parameters were studied: total cholesterol level and erythrocyte membrane fluidity, lipid peroxidation, SH groups in membrane protein and plasma lipids.
Results. We observed a decrease in TC (20%), LDL-C (35%), level of lipid peroxidation (25%) and total cholesterol in erythrocytes (23%), and an increase in HDL-C (8%) and erythrocyte membrane fluidity of subsurface layers (14%) after 6 months of 10 mg atorvastatin + 10 mg ezetimibe therapy, in comparison with healthy controls. In the group treated with 40 mg atorvastatin for 6 months, decreased LDL-C (23%), lipid peroxidation (37%) and membrane cholesterol concentration (18%) was noted, as well as an increase in erythrocyte membrane fluidity in the subsurface layers (12%).
Conclusion. Both the combination therapy and the monotherapy lead to an improvement of erythrocyte membrane structure, whose parameters reached values close to those in the control healthy group.
coronary artery disease, statins, total cholesterol, membrane fluidity, ezetimibe
- Jones P, Kafonek S, Laurora I, Hunninghake D: Comparative dose efficacy study of atorvastatin versus simvastatin, pravastatin, lovastatin, and fluvastatin in patients with hypercholesterolemia (the CURVES study). Am J Cardiol 1998, 81, 582–587.
- Garcia-Calvo M, Lisnock J, Bull HG, Hawes BE, Burnett DA, Braun MP, Crona JH, Davis HR Jr, Dean DC, Detmers PA, Graziano MP, Hughes M, Macintyre DE, Ogawa A, O’Neill KA, Iyer SP, Shevell DE, Smith MM, Tang YS, Makarewicz AM, Ujjainwalla F, Altmann SW, Chapman KT, Thornberry NA: The target of ezetimibe is Niemann-Pick C1-Like 1 (NPC1L1). Proc Natl Acad Sci U S A 2005, 102, 8132–8137.
- Koter M, Franiak I, Strychalska K, Broncel M, Chojnowska-Jezierska J: Damage to the structure of erythrocyte plasma membranes in patients with type-2 hypercholesterolemia. Int J Biochem Cell Biol 2004, 36, 205–215.
- Tziakas DN, Kaski JC, Chalikias GK, Romero C, Fredericks S, Tentes IK, Kortsaris AX, Hatseras DI, Holt DW: Total cholesterol content of erythrocyte membranes is increased in patients with acute coronary syndrome: A new marker of clinical instability? J Am Coll Cardiol 2007, 49, 2081–2089.
- Stocks J, Dormandy TL: The autooxidation of red cell lipids by hydrogen peroxide. B J Haematol 1971, 20, 95–111.
- Dodge JT, Mitchell C, Hanahan DJ: The preparation and chemical characteristics of hemoglobin – free ghost of human erythrocytes. Arch Biochem Biophys 1963, 100, 119–130.
- Ellman G: Tissue sulfhydryl groups. Arch Biochem Biophys 1959, 82, 70–77.
- Drabkin DL: The crystallographic and optical properties of the hemoglobin of men in comparison with those of other species. J Biol Chem 1946, 164, 703–723.
- Lowry OH, Rosebrough A, Ferr L, Randall RJ: Protein measurement with the Folin Phenol reagent. J Biol Chem 1951, 193, 265–275.
- Rodriguez-Vilo F, Martinez-Caynela M, Zafra MF, Garcie-Peregin F, Ramirez HA: Procedure for the simultaneous determination of lipid and protein in biomembranes and other biological samples. Lipids 1991, 26, 77–80.
- Shinitzky M, Barenholz Y: Fluidity parameters of lipid regions determined by fluorescence polarization. Biochim Biophys Acta 1978, 515, 367–394.
- Broncel M, Balcerak M, Bała A, Koter-Michalak M, Duchnowicz P, Chojnowska-Jezierska J: Struktura błon erytrocytów u pacjentów z mieszaną hiperlipidemią. Wiad Lek 2007, 60, 4–9.
- Koter M, Broncel M, Chojnowska-Jezierska J, Klikczynska K, Franiak I: The effect of atorvastatin on erythrocyte membranes and serum lipids in patients with type 2 hypercholesterolemia. Eur J Clin Pharmacol 2002, 58, 501–506.
- Broncel M, Bała A, Koter-Michalak M, Duchnowicz P, Wojsznis W, Chojnowska-Jezierska J: Physicochemical modifications induced by statins therapy on human erythrocytes membranes. Wiad Lek 2007, 60, 321–328.
- Zhong Y, Tang H, Zeng Q, Wang X, Yi G, Meng K, Mao Y, Mao X: Total cholesterol content of erythrocyte membranes is associated with the severity of coronary artery disease and the therapeutic effect of rosuvastatin. Ups J Med Sci 2012, 117, 390–398.
- Koter M, Franiak I, Broncel M, Chojnowska-Jezierska J: Effects of simvastatin and pravastatin on peroxidation of erythrocyte plasma membrane lipids in patients with type 2 hypercholesterolemia. Can J Physiol Pharmacol 2003, 81, 485–492.
- Coccia R, Spadaccio C, Foppoli C, Perluigi M, Covino E, Lusini M, Chello M: The effect of simvastatin on erythrocyte membrane fluidity during oxidative stress induced by cardiopulmonary bypass: A randomized controlled study. Clin Ther 2007, 29, 1706–1717.
- Martinez-Sanchez G, Delgado-Roche L, Diaz-Batista A, Perez-Davison G, Re L: Effects of ozone therapy on haemostatic and oxidative stress index in coronary artery disease. Eur J Pharmacol 2012, 691, 156–162.
- Walter MF, Jacob RF, Jeffers B, Ghadanfar MM, Preston GM, Buch J, Mason RP: Serum levels of thiobarbituric acid reactive substances predict cardiovascular events in patients with stable coronary artery disease. J Am Coll Cardiol 2004, 44, 1996–2002.
- Uydu HA, Yıldırmıs S, Orem C, Calapoglu M, Alver A, Kural B, Orem A: The effects of atorvastatin therapy on rheological characteristics of erythrocyte membrane, serum lipid profile and oxidative status in patients with dyslipidemia. J Membrane Biol 2012, 245, 697–705.
- Aydin S, Uzun H, Sozer V, Altug T: Effects of atorvastatin therapy on protein oxidation and oxidative DNA damage in hypercholesterolemic rabbits. Pharmacol Res 2009, 59, 242–247.
- Padhy BM, Yadav R, Gupta YK: Hypolipidaemic and anti-inflammatory effects of fixed dose combination of atorvastatin plus ezetimibe in Indian patients with dyslipidaemia. Singapore Med J 2013, 54, 90–95.
- Kastelein JJ, Akdim F, Stroes ES, Zwinderman AH, Bots ML, Stalenhoef AF, Visseren FL, Sijbrands EJ, Trip MD, Stein EA, Gaudet D, Duivenvoorden R, Veltri EP, Marais AD, de Groot E: ENHANCE Investigators. Simvastatin with or without ezetimibe in familial hypercholesterolemia. N Engl J Med 2008, 358, 1431–1443.
- Cannon CP, Blazing MA, Giugliano RP, McCagg A, White JA, Theroux P, Darius H, Lewis BS, Ophuis TO, Jukema JW: Ezetimibe added to statin therapy after acute coronary syndromes. N Engl J Med 2015, 372, 2387–2397.